# data[].attributes.headline
OK, two groups submitted. We want more group to share the isolated components yeah!

# data[].attributes.subject
OK, two groups submitted. We want more group to share the isolated components yeah!

# data[].attributes.headline
Week 3 (izzani, balqis, marsha, syafika, izzati) (k2)

# data[].attributes.subject
Week 3 (izzani, balqis, marsha, syafika, izzati) (k2)

# data[].attributes.body
The Alkaloids and Bioactivities of Ethanol Extract from a Traditional Remedy of Vietnam

compound names:
1) palmatine
2) berberine

Source and reference :

http://www.eurekaselect.com/168727/article

# data[].attributes.headline
Week 3 (rohar, yasmin, raja, nurin, alya, sim) (K2)

# data[].attributes.subject
Week 3 (rohar, yasmin, raja, nurin, alya, sim) (K2)

# data[].attributes.body
Chemical composition, antioxidant and antibacterial activities of Tamarix balansae J. Gay aerial parts
compund involve :
1) Afzelin
2) rhamnocitrin

source & references
https://www.sciencedirect.com/science/article/abs/pii/S1043661819311533

# data[].attributes.headline
Week 3 (Chan kiki,Chi Ying,Mirza,Arlina)

# data[].attributes.subject
Week 3 (Chan kiki,Chi Ying,Mirza,Arlina)

# data[].attributes.body
Natural products: Potential lead compounds for the treatment of endometriosis

Compound involve:
1. Ginsenoside Rf

2. Curcumin

Source and references:
https://www.sciencedirect.com/science/article/pii/S0301211519305342

# data[].attributes.headline
Week 3 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

# data[].attributes.subject
Week 3 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

# data[].attributes.body
Application of a Catalytic Asymmetric Povarov Reaction using Chiral Ureas to the Synthesis of a Tetrahyroquinoline Library

Compounds involve:
1) martinelline
2) oxamniquine

Source and reference:
https://www.researchgate.net/figure/Examples-of-natural-products-and-biologically-active-compounds-featuring-a_fig1_232609256

# data[].attributes.headline
Week 3 (Rafiqah, Haiffa, Atika, Izzati Sharif, Adilah)

# data[].attributes.subject
Week 3 (Rafiqah, Haiffa, Atika, Izzati Sharif, Adilah)

# data[].attributes.body
Natural Products in Drug Discovery

Compound names :
1) Paclitaxel
2) Pseudohypericin

Source and Reference :
https://www.intechopen.com/books/pharmacognosy-medicinal-plants/natural-products-in-drug-discovery

# data[].attributes.body
Alya, syikin, syiba, fara, rabiatul
Biocarbon from peanut hulls and their green composites with bionased poly(trimethlene terephthalate) (ptt)

Material
Peanuts hulls
https://www.nature.com/articles/s41598-020-59582-3.pdf

# data[].attributes.headline
Week 3 (damiya,huda,aina,farhah, saran) (k2)

# data[].attributes.subject
Week 3 (damiya,huda,aina,farhah, saran) (k2)

# data[].attributes.body
A CONTINUING SOURCE OF NOVEL DRUG LEADS

Compounds names:
1) khellin
2) sodium chromoglycate
3) galegine
4) metformin
5) papaverine
6) verapamil

Source & Reference:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672862/

# data[].attributes.headline
Week 4 (Rafiqah, Haiffa, Atika, Izzati Sharif, Adilah)

# data[].attributes.subject
Week 4 (Rafiqah, Haiffa, Atika, Izzati Sharif, Adilah)

# data[].attributes.body
Konamycins A and B and Rubromycins CA1 and CA2, Aromatic Polyketides from the Tunicate-Derived Streptomyces hyaluromycini MB-PO13T.

Compounds names :
1. Konamycins A and B
2. Rubromycins CA1 and CA2

Source and References :
Harunari, E., Imada, C., & Igarashi, Y. (2019). Konamycins A and B and Rubromycins CA1 and CA2, Aromatic Polyketides from the Tunicate-Derived Streptomyces hyaluromycini MB-PO13T [Review-article]. Journal of Natural Products, 82(6), 1609–1615.
https://doi.org/10.1021/acs.jnatprod.9b00107

# data[].attributes.headline
week 4 ( Syafika , Izzani, Marsha, Balqis , Izzati )(k2)

# data[].attributes.subject
week 4 ( Syafika , Izzani, Marsha, Balqis , Izzati )(k2)

# data[].attributes.body
Access to new highly potent antileukemia, antiviral and antimalarial agents via hybridization of natural products (homo)egonol, thymoquinone and artemisinin

compound names :
1. dihydroartemisinin
2. artesunic acid
3. egonol
4. homoegonol
5. artemisinin
6. thymoquinone
7. chloroambucil

source & reference:
https://www.sciencedirect.com/science/article/pii/S0968089618307004

# data[].attributes.headline
Week 5 (Group Aaron, Vatsala, Jin Min, Jing Rou & CK) (K2)

# data[].attributes.subject
Week 5 (Group Aaron, Vatsala, Jin Min, Jing Rou & CK) (K2)

# data[].attributes.body
Isolation of terpenoids from Pimpinella anisum essential oil by high-performance counter-current chromatography

Compounds name :
1. linalool
2. terpinen-4-ol
3. alpha-terpineol

# data[].attributes.headline
Week 3 (syakilla,fatnin, anis,vannisree,nadirah husna) (k2) Natural products: Potential lead compounds for the treatment of endometriosis

# data[].attributes.subject
Week 3 (syakilla,fatnin, anis,vannisree,nadirah husna) (k2) Natural products: Potential lead compounds for the treatment of endometriosis

# data[].attributes.body
Compounds name:
1. Curcumin
2.Ginsenoside Rf
3.Alpha-lipoic acid mixture
4.Melatonin
5.Scutellarin
6.Crocin
7.Genistein
8.Daidzein-rich isoflavone aglycones
source and reference of the compound
https://www.sciencedirect.com/science/article/pii/S0301211519305342

# data[].attributes.headline
Week 4 (Group Aaron, Vatsala, Jin Min, Jing Rou,CK) (K2)

# data[].attributes.subject
Week 4 (Group Aaron, Vatsala, Jin Min, Jing Rou,CK) (K2)

# data[].attributes.body
Antioxidant and anticholinesterase potential of Ferulago cassia with farther bio-guided isolation of active coumarin constituents

Compounds being isolated
1) peucedanol
2) suberosin
3) grandivitinol
4) umbelliferone

# data[].attributes.attachment_link.readable_text
Highlights

*

Antioxidant-anticholinesterase potential of Ferulago cassia by bioguided isolation.

*

The TBA antioxidant activity results of extract were higher compared to the standards.

*

Root and fruit got the highest total phenolics and DPPH antioxidant potential.

*

Peucedanol, suberosin, umbelliferone indicated strong anticholinesterase activity.

*

It can be used as promising herb for pharmaceutical products.

Abstract

Ferulago species are utilized as flavor, sedative, tonic, aphrodisiac, peptic, immunostimulant, antibronchitis, vermicidal, carminative and for the curation of cancers and skin disorders in Middle Eastern region. The presented research reports anticholinesterase and antioxidant capacities of aerial parts, fruits, flowers, roots extracts and isolated coumarins of roots from of Ferulago cassia Boiss (peucedanol ( 1), suberosin ( 2), grandivitinol ( 3) and umbelliferone ( 4)). The TBA antioxidant activity results of some samples were strong when compared the references rutin, propyl gallate and chlorogenic acid. The highest phenolics level and DPPH antioxidant capacity were determined in fraction from root and fruit. Among different studied extract fractions, the CH ₂Cl ₂ fractions, especially root and fruit, has been detected to indicate considerable acetylcholinesterase (AChE) (53.24%) and butyrylcholinesterase (BuChE) (96.56%) inhibition at 20 μg/mL, respectively. Peucedanol (76.22%) and suberosin (71.67%) indicated strong inhibition towards BuChE. The umbelliferone (61.09%) exhibitted strong inhibition towards AChE at 20 μg/mL. F. cassia can be used a potency for pharmaceutical products which have antioxidant and anticholinesterase activity.

View full text

# data[].attributes.attachment_link.title
Antioxidant and anticholinesterase potential of Ferulago cassia with farther bio-guided isolation of active coumarin constituents

# data[].attributes.attachment_link.description
Antioxidant-anticholinesterase potential of Ferulago cassia by bioguided isolation. * The TBA antioxidant activity results of extract were higher compared to the standards. * Root and fruit got the highest total phenolics and DPPH antioxidant potential. * Peucedanol, suberosin, umbelliferone indicated strong anticholinesterase activity. * It can be used as promising herb for pharmaceutical products.

# data[].attributes.headline
week 4 (Aina,najwa,saran,huda dan damia)

# data[].attributes.subject
week 4 (Aina,najwa,saran,huda dan damia)

# data[].attributes.body
Post-column in-source derivatisation in LC-MS: a tool for
natural products characterisation and metabolomics

compound involve:
-cyloartanes
-cynamin

https://onlinelibrary.wiley.com/doi/abs/10.1002/pca.2926?af=R

# data[].attributes.headline
Week 4 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

# data[].attributes.subject
Week 4 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

# data[].attributes.body
The first synthesis of phenylpropanoid derivative bromophenols including natural products: Formation of an indene derivative compound

Compounds names :
1.  red algae Rhodomela confervoides
2. Symphyocladia latiuscula

Source & reference :
https://www.sciencedirect.com/science/article/pii/S0040402020301186

# data[].attributes.headline
week 4 (syakillla, fatnin, anis, nadirah, husna, vannisree) (k2) A review of the literature and latest advances in research of Piper sarmentosum.

# data[].attributes.subject
week 4 (syakillla, fatnin, anis, nadirah, husna, vannisree) (k2) A review of the literature and latest advances in research of Piper sarmentosum.

# data[].attributes.body
compounds name :
1. pellitorne
2. sarmentine
3. 1-piperettyl pyorrolidine
4. guneensine
5. brachyamide B
6. brachystamide

source and references :
https://www.tandfonline.com/doi/ref/10.3109/13880209.2011.654229?scroll=top

# data[].attributes.attachment_link.title
A review of the literature and latest advances in research of Piper sarmentosum

# data[].attributes.body
Week 5 (Marsha, Balqis, Ika, Izzani, Zatisha) (K2)

Isolation and structure elucidation of cyclopeptide alkaloids from the leaves of Heisteria parvifolia.

Compound names:
1) cycloheisterin
2) anorldianine

Source & Reference:
https://www.sciencedirect.com/science/article/pii/S0031942219302468

# data[].attributes.headline
Week 5, ( group saran,aina,najwa, huda,damiya)

# data[].attributes.subject
Week 5, ( group saran,aina,najwa, huda,damiya)

# data[].attributes.body
Anticancer activity of natural compounds from plant and marine environment

Compounds name
1) camptothecin
2) podophyllotoxin
3) geniposide
4) colchicine

Source and reference

# data[].attributes.attachment_link.readable_text
Abstract

This paper describes the substances of plant and marine origin that have anticancer properties. The chemical structure of the molecules of these substances, their properties, mechanisms of action, their structure-activity relationships, along with their anticancer properties and their potential as chemotherapeutic drugs are discussed in this paper. This paper presents natural substances from plants, animals, and their aquatic environments. These substances include the vinca alkaloids, mistletoe plant extracts, podophyllotoxin derivatives, taxanes, camptothecin, combretastatin, and others including geniposide, colchicine, artesunate, homoharringtonine, salvicine, ellipticine, roscovitine, maytanasin, tapsigargin, and bruceantin. Compounds (psammaplin, didemnin, dolastin, ecteinascidin, and halichondrin) isolated from the marine plants and animals such as microalgae, cyanobacteria, heterotrophic bacteria, invertebrates (e.g., sponges, tunicates, and soft corals) as well as certain other substances that have been tested on cells and experimental animals and used in human chemotherapy.

Keywords: natural compounds, anticancer properties, substances from marin

1. Introduction

The development of cancer registries throughout the world has led to a search for novel drugs that are toxic to the cancer cells while having no harmful effect on normal cells. The anticancer drugs used previously exhibited relatively high toxicity not only to the tumour cells, but also to the normal cells of the body part in which the cancer had developed. Currently, the search for novel anticancer drugs is being conducted among terrestrial plants, as well as in marine environments [ 1]. Plants have been used for centuries to treat diseases. In various parts of the world, several plants are consumed for their health benefits as a part of traditional folk medicine. The increase in the incidence of various types of cancer creates a need for new anticancer drugs. For example, in 2017, 1,688,780 new cancer cases and 600,920 cancer deaths are projected to occur in the United States [ 2]. Numerous anticancer drugs isolated from plant materials are tested on cells (including various cancer cell lines) and experimental animals after purification and then sent to clinical trials. In recent years, there has been a dynamic increase in the number of newly discovered natural compounds. In 2006, about 50,000 such substances were known, whereas, in 2014, the number of the newly discovered molecules increased to approximately 326,000. Among these, there were approximately 170,000 compounds in the toxicity class. In addition, there are 195,000 pharmacologically active compounds for which the interactions are quantitatively known [ 3]. Plants that have been used in traditional medicine for centuries have found application as sources of materials that possess high biological activity [ 4]. One approach is to obtain these substances through extractions from the plant materials. Another approach is to use biotechnological tools to produce plant-derived anticancer compounds. The substances of natural origin (e.g., from plants and aquatic animals) that exhibit antitumour properties belong to various groups of compounds, such as alkaloids, diterpenes, diterpenoquinone, purine-based compounds, lactonic sesquiterpene, peptides, cyclic depsipeptide, proteins, macrocyclic polyethers, etc. Sometimes, the cost of extraction of these substances from natural materials is much lower than the cost of their chemical synthesis. In the case of artemisinin, the low cost of the extraction process has been described: 250 kg of leaves yields 4 to 5 kg of raw artemisinin extract, which yields about 1 kg of pure artemisinine [ 5]. However, obtaining 50 grams of crude vincristine sulphate requires about 1 tonne of Catharanthus roseus leaves. However, vinblastine, which is present in Catharanthus roseus, occurs at a level that is 1000 times higher than vincristine and its cost is one-third of that of vincristine. Vinblastine is used as the parent drug to obtain vincristine [ 6]. In turn, paclitaxel is isolated from the yew tree or semisynthesized from its precursors, such as baccatin III and 10-deacetylbaccatin III, which are all isolated from this natural plant [ 7]. However, obtaining it from the tree bark leads to a reduction in the natural resources of these trees. Additionally, isolation from the Pacific yew tree yields a low concentration of the drug-only 100 mg of Taxol per kg of the bark [ 8]. Taxanes can also be extracted from the renewable and more readily available leaves of the European yew tree. To protect Taxus, methods for the synthesis of these compounds have been developed. Two independent research teams, Holton (1994) [ 9] and Nikolau (1994) [ 10], developed independent methods of paclitaxel synthesis [ 10, 11]. In the year 1996, they were joined by Danishefsky (1996) [ 12], who developed another way to synthesize this taxane. Paclitaxel and docetaxel are used widely as monotherapies of breast cancer as well as in combination with other anticancer drugs, such as the combination of docetaxel with either cisplatin or carboplatin (also in ovarian cancer), and lately, bevacizumab [ 13, 14, 15]. Numerous natural products presented in this paper are modified by introduction of the nitroxide residue, which, in many cases, increases their anticancer activity [ 16]. The work describes the compounds of plant origin, their occurrence and variety of mechanisms of action, e.g., binding to microtubules, topoisomerase inhibition, binding to DNA, cell-cycle arrest, and apoptosis. Their properties have been tested on various cancer cell lines, experimental animals, and in human chemotherapy. The presented substances can be used alone or in combination with other antineoplastic agents of natural origin or with synthesized drugs. The work presents known anticancer drugs that have been approved for use, as well as new analogies and other less known substances with anti-cancer properties that may be considered as potential chemotherapy drugs. The uses, mechanisms of action, and doses of natural compounds from plants and the marine environment are presented in and , respectively.

Table 1

Catharanthus alkaloids

Catharanthus roseus Pink

acute lymphocytic leukaemia,
non-small cell lung cancer,
bladder cancer

inhibit the microtubule dynamics and stabilise them
disintegrate the microtubules and damage the mitotic spindle, leading to the inhibition of mitosis and causing apoptosis

Viscum Album extract

Viscum album-Mistletoe plant
Viscum album that are used in therapy are usually a mixture of the extracts obtained from various host trees (oak, apple, pine, fir, willow, birch, lime, etc.).

human colon cancer cells (Colo 320 HSR)
breast cancer cells (MFM-223, HCC-1937, KPL-1, MCF-7)

activation of the intrinsic (activated Caspase-2 and 9) extrinsic (activated Caspase-2, 3 and 8) pathways of apoptosis
activation of only the mitochondrial pathway of apoptosis
early cell-cycle inhibition followed by apoptosis
activation of the mitochondrial pathway of apoptosis

Combretastatin

Combretum caffrum - "African willow"

human thyroid papillary carcinoma cell (TPC1)

>5 µM

binds to β-tubulin at what is known as the colchicine site
causes the destabilisation of the microtubules

Podophyllotoxins

Podophyllum peltatum, Podophyllum emodi
Podophyllum versipelle, Linum
Juniperus

small-cell lung cancer (SCLC)

>1 µg/mL
(etoposide)

disrupt the organisation of the karyokinetic spindle
single-strand and double-strand breaks in DNA through their interactions with DNA topoisomerase II
induce cell cycle arrest in the G2-phase of the cell cycle

Geniposide and its derivatives

Gardenia jasminoides Ellis-Rubiaceae

human non-small-cell lung cancer H1299 cell

activation of the mitochondrial execution pathway by Caspase-9 and -3
increase levels of Bax in response to p38MAPK signalling
initiation of the mitochondrial death cascade

Colchicine

Colchicum genus (e.g., the autumn crocus, Colchicum autumnale, also known as "meadow saffron")

hepatocellular carcinoma HepG2

10 μM

depolymerises the microtubules at high concentrations
stabilizes the microtubule dynamics at low concentrations
limits mitochondrial metabolism in cancer cells

Homoharrigtonine

Cephalotaxus-Cephalotaxaceae ( C. harringtonia K. Koch, C. haianensis qinensis)

gallbladder adenocarcinoma cell line (Mz-ChA-1),
colorectal adenocarcinoma cell line (HT-29)

blocks synthesis in the peptidyl transferase centre

Salvicine

Salvia pronitis Hance-Labiatae

leukaemia cell (P388, HL-60), stomach cancer cell (SGC-7901)

breaks two strands of DNA by facilitating TOP2 activity
inhibits re-ligation

Elipticine

Ochrosia elliptica Labill

leukaemia (HL-60, CCRF-CEM) cells

disrupts the cell-cycle by regulating the expression of some kinases (cyclin B1 and Cdc2)
generates free radicals

Roscovitine

Raphanus sativus L.-Brassicaceae

highly metastatic and invasive breast cancer cells MDA-MB231

10 μg/mL

inhibits cyclin-dependent kinase (CDK) activity, which preferentially inhibits numerous target enzymes such as CDK1, CDK2 and CDK5 leading to cell-cycle arrest in the G1 and G2 phases

Tapsigargin

Thapsia garganica L. -Apiaceae

mouse embryonic fibroblast (MEF) cells

3 μM

inhibits sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) in the sarco/endoplasmic reticulum, raises the intracellular calcium concentration,
enhances the endoplasmic reticulum stress, caspase activation,
releases apoptotic factors from the mitochondria and directly activates the calcium-dependent endonucleases,
inhibits the fusion of autophagosomes with lysosomes

Bruceantin

Brucea antidysenterica-Simaroubacea, Brucea javanica -Fructus Bruceae

human pancreatic cancer cells (PANC-1, SW1990)

inhibits protein synthesis through interaction with peptidyltransferase, which blocks the formation of peptide binding

Table 2

Psammaplin

Poecillastra sp.,
Jaspis sp., Psammaplin aplysilla
marine microalgae,
cyanobacteria,
heterotrophic bacteria living in association with the invertebrates (e.g., sponges, tunicates, and soft corals)

human endometrial Ishikawa cancer cells

5 μg/mL

antiproliferative effects,
selectively induces genes related to cell-cycle arrest and apoptosis
inhibits the activity histone deacetylase (HDAC), chitinase topoisomerase II, farnesyl-protein transferase, leucine aminopeptidase,

Ecteinascidin

Ecteinascidia turbinata,
Pseudomonas fluorescens

L1210 leukaemia cells

binds in the minor groove of DNA to induce an unprecedented bend in the DNA helix towards the major groove
interferes with cellular transcription-coupled nucleotide excision repair to induce cell death and cytotoxicity

2. The Catharanthus Alkaloids

The Catharanthus (or Vinca) alkaloids (CAs or VAs) comprise a group of about 130 terpenoid indole alkaloids [ 5]. Vinblastine was the first alkaloid isolated by the Canadian scientists Robert Noble and Charles Beer from the Madagascar periwinkle plant in the 1950s. One group of medicines of plant origin is vincristine and its derivatives, which are heterodimeric (indoloid) alkaloids formed during the biosynthesis of vindoline and catharanthine that are present in pink Catharanthus roseus. Other Catharanthus species such as C. longifolius, C. trichophyllus and C. lanceus contain vindoline type alkaloids. These medicines demonstrate a cytostatic effect, destroying the living cells [ 17]. This group includes vincristine (1), vinblastine (2), anhydrovinblastine, and the semisynthetic derivatives vindesine (3), vinorelbine (navelbine) (4), and vinflunine (5) (the fluorinated analogue of vinorelbine) (). The mechanism of the cytotoxic action of the Catharanthus alkaloids is associated with their effects on the microtubules. Microtubules are the cytoskeletal structures that are composed of the heterodimers of α-tubulin and β-tubulin, which exhibit dynamics that are manifested inter alia by the alternating elongation and shortening of their ends [ 18, 19]. Microtubules form the mitotic spindle, which performs an important role in the process of mitosis. Therefore, microtubules are a suitable target for several anticancer drugs, including the vinca alkaloids, which bind to the β-subunit of the tubulin heterodimers [ 20, 21]. The Catharanthus alkaloids demonstrate different mechanisms of action depending on their concentration. Low concentrations (<1 μmol) inhibit the microtubule dynamics and stabilise them, whereas, high concentrations (>1-2 μmol) disintegrate the microtubules and damage the mitotic spindle, leading to the inhibition of mitosis and consequently, to apoptosis [ 22]. Catharanthus alkaloids are among the most widely used chemotherapy reagents for various tumour therapies; however, they exhibit side effects. To reduce their toxicity and enhance the therapeutic efficiency of these compounds, liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations were used [ 23]. Catharanthus alkaloids are used in chemotherapy to treat breast cancer, ovarian cancer, non-small cell lung cancer, and soft tissue sarcoma (orphan). They are also used in the treatment of acute lymphocytic leukaemia, malignant lymphomas, including Hodgkin's lymphoma and non-Hodgkin's lymphoma, multiple myeloma, idiopathic thrombocytopenic purpura and solid tumours, including metastatic testicular cancer, Ewing's sarcoma, foetal rhabdomyosarcoma, primary neuroectodermal tumours (such as enucleus, nucleus, or neuroblastoma), Wilms' tumour, and retinoblastoma [ 20, 21]. Vinblastine and vinflunine are semisynthetic Catharanthus alkaloids [ 24]. For example, vinflunine is used in the treatment of bladder cancer. Vindesine is used mainly in the treatment of acute lymphocytic leukaemia and less frequently in the treatment of breast cancer, colorectal cancer, non-small cell lung cancer (NSCLC), and renal cancer. Vinorelbine is used in the treatment of non-small cell lung cancer. Catharanthus alkaloids are used in combination with other antineoplastic agents, for example, vinblastine is used with doxorubicin, bleomycin, and dacarbazine (standard chemotherapy for Hodgkin lymphoma) [ 25] and vincristine is used in combination with bleomycin, etoposide, doxorubicin, cyclophosphamide, procarbazine, and prednisone (Scheme of German Hodgkin Study Group developed a dose-escalated and accelerated combined modality regimen) [ 22], vinorelbine, and cisplatin (stage III A and stage III B non-small cell lung cancer) [ 26, 27]. Lately, it has been shown that vincristine in combination with procarbazine and lomustine plus radiotherapy is more effective for glioma treatment than radiotherapy alone [ 28]. However, in addition to their valuable anticancer actions, these drugs, unfortunately, cause several side effects.

3. Viscum Album Extract

Another group of plant medicines includes viscotoxins (VT) and lectins isolated from the mistletoe plant ( Viscum album); these medicines exhibit cytotoxic effects. Viscotoxins are present in the extracts isolated from the common mistletoe plant. Different forms of this drug may be obtained depending on the species of the tree on which the mistletoe grows. The medicinal preparations are available from a variety of host trees, such as oak, apple, pine, fir, willow, birch, lime, etc. The medicinal preparations obtained from Viscum album that are used in therapy are usually a mixture of the extracts obtained from various host trees. For example, one extract can come from various trees such as fir, apple tree, and pine, while another one can contain extracts from the apple tree, oak, and elm. Other medicinal preparations from mistletoe are used in the treatment of a different kind of cancer. The healing effects observed with the use of these extracts are usually more visible with the use of whole extracts rather than the use of purified mistletoe lectins and viscotoxins alone. Viscum album extract (VAE) contains the proteins known as lectins (mistletoe lectins, ML), namely ML-1, ML-2, and ML-3, the glycoprotein that binds to d-galactose and N-acetyl-d-galactosamine, viscotoxins, oligosaccharides, polysaccharides, and alkaloids [ 29]. VAE also contains flavonoids, such as quercetin and quercetin methyl ethers, kaempferol and a few of its methyl derivatives, and rarely, naringenin [ 30]. Viscotoxins are peptides with a molecular weight of approximately 5000 g/mol; they are rich in cysteine and belong to the class of plant thionins. They are toxic to a variety of cell types. It was demonstrated that viscotoxin and mistletoe lectin I exhibit toxic effects on three tumour cell lines-the Yoshida sarcoma cell line, the T-cell leukaemia cell line Molt4, and the myeloid leukaemia cell line K562. Yoshida sarcoma cells are more sensitive to viscotoxin while the human leukaemia cell line K562 is more sensitive to the mistletoe lectin [ 31]. In addition to the isolated lectins, viscotoxin oligosaccharides are also suspected to play a role in the biological activity of crude Viscum album extracts. VAE and its constituent compounds have strong cytotoxic effects on cancer cells in vitro. It has been reported that lectins are able to induce apoptosis. This process occurs together with the direct or indirect killing of the cells via damage to their cell membranes with the subsequent influx of calcium. It was also suggested that the damage caused to the membrane integrity may lead to the release of calcium from the cells and the activation of DNA-cleaving endonucleases [ 29]. It has been observed that the four bladder carcinoma cell lines (T-24, TCC-SUP, UM-UC-3, and J-82) are more sensitive to mistletoe preparations compared to the four breast carcinoma cell lines (MCF-7, MFM-223, KPL-1 and HCC-1937). In Dukes' type C colorectal adenocarcinoma cell line Colo 320 HSR, VAE caused the activation of intrinsic (activated Caspase-2 and Caspase-9) and extrinsic (activated Caspase-2, Caspase-3 and Caspase-8) pathways of apoptosis [ 32]. In the colon cancer cell lines Caco-2 and HT-29, apoptosis was induced by the activation of only the mitochondrial pathway [ 33]. Similar results were obtained for the lung cancer cell lines MR 65, NCI-H125 and NCI-H82, where Viscum album extracts caused early dose-dependent cell cycle inhibition followed by apoptosis. However, the cytotoxicity test results revealed different responses in various breast cancer cell lines (Kpl-1, MCF-7 and Mfm-223) to the mistletoe preparations from different host trees [ 34]. Apoptosis was induced by the activation of its mitochondrial pathway [ 33]. The application of Viscum album extracts was demonstrated to increase the survival rate and tumour remission in various breast cancer and gynaecological cancer models especially in mice, while the application in rats demonstrated mixed results [ 35]. In vivo studies have demonstrated that the injection of Viscum album extract in patients with breast cancer leads to an increase in the number of neutrophils and the activation of the phagocytic cells. During a long-term therapy, another Viscum album preparation led to an increase in the number of B CD19+, Th CD4+, T CD8+, Tc CD8+ and CD28+, and NK CD16+/CD56+ cells within two to three months of therapy [ 36]. These drugs or extracts have found applications in the treatment of oral cavity, larynx, throat, and breast cancers. Moreover, the extracts were used in the adjuvant therapy for cancer because of their immunostimulatory and cytotoxic properties [ 37]. These effects are usually more evident with the use of the whole extracts, rather than the use of the purified mistletoe lectins and viscotoxins alone [ 29].

4. Taxanes

Paclitaxel (PTX) (6) belongs to the group of drugs obtained from the European yew ( Taxus baccata) and/or the Pacific yew ( Taxus brevifolia) tree needles. It belongs to a group of compounds known as taxanes, which are mitosis inhibitors. Paclitaxel and its semisynthetic derivatives docetaxel (DTX) (7) and cabazitaxel (CTX) (8) are derived from 10-baccatin III or 10-deacetylbaccatin III (both contain characteristics of the taxane skeleton-three condenset homocyclic rings and one heterocyclic ring) ().

Although the full synthesis of paclitaxel has been described, there are still other methods for isolating taxanes from natural materials such as Arabidopsis, Nicotian sylvestric, or endophytic fungi, but these materials contain low concentrations of taxanes [ 38]. An interesting way to produce paclitaxel is plant cell fermentation. It is an effective and efficient method developed by Lin and colleagues that does not require the collection of natural products. The natural production of paclitaxel from Taxus is environmentally unsustainable and economically unfeasible. Lately, a method of synthesizing the precursor of paclitaxel 10-deacetylbaccatin III has been developed in the bioengineering sector [ 39]. Paclitaxel and docetaxel are used widely as monotherapies, as well as in combination with other anticancer drugs that inhibit mitosis and participate in cell apoptosis. However, both taxanes demonstrate differences in their toxicity profiles [ 40]. The anticancer activity of taxanes is similar to the action of vinca alkaloids and is associated with their effect on the microtubules, which are composed of heterodimers of α-tubulin and β-tubulin. Taxanes, however, constitute the second group of microtubule-interacting agents-microtubule-stabilising agents that stimulate the microtubule polymerization [ 18]. The processes of microtubule polymerisation and depolymerisation are essential for mitotic cell division. Taxanes, as opposed to vinca alkaloids, bind with high affinity to the inside of the microtubules. High concentrations of taxanes lead to microtubule polymerisation, while the Catharanthus alkaloids inhibit it. Taxanes are one of the most effective drug types used in the treatment of breast and ovarian cancers; they are also used to treat squamous cell carcinoma of head and neck [ 41]. Taxanes may be used as single agents or in combination with the anthracyclines, antimetabolites, and vinca alkaloids or even in combination with each other to provide benefits in the treatment of women with HR-negative metastatic breast cancer (MBC). To treat women with HER2-positive disease, the taxanes are administered along with trastuzumab, vinorelbine, or capecitabine. Trastuzumab is a monoclonal antibody that is also used in the treatment of breast cancer and metastatic gastric or gastroesophageal cancer. However, different levels of synergism have been observed between each taxane and trastuzumab [ 42]. The novel drugs that are being used in the metastatic therapy are the nanoparticle albumin-bound paclitaxel in MBC, and the propane-1,2,3-triol complex, which was initially approved for the treatment of relapsed ovarian cancer. The use of docetaxel in MBC therapy was ground-breaking, especially after the failure of using anthracyclines for this purpose. The application of docetaxel also yields better results than the use of mitomycin along with vinblastine. Given the high mortality rate of the disease, the treatment of breast cancer holds great importance in the field of medicine. The choice of treatment depends on the stage of cancer invasiveness (I, II, or III) from the non-invasive cancer stage (ductal carcinoma in situ). Metastatic breast cancer (stage IV) spreads from the nearby lymph nodes to other parts of the body. Paclitaxel is used in the treatment of breast and ovarian cancers, non-small cell lung cancer, and Kaposi's sarcoma [ 43, 44]. A combination of bevacizumab and paclitaxel exhibits synergetic effects, anti-tumour efficacy, and a satisfactory toxicity profile in tpatients with breast cancer and in patients with non-small cell lung cancer [ 45]. Paclitaxel may be used alone or in combination with other anticancer drugs, such as cisplatin or carboplatin [ 46, 47]. In the treatment of ovarian cancer, dual therapy with docetaxel and camptothecin, as well as docetaxel in combination with gemcitabine, has demonstrated promising results as a second-line therapy. Similar results were obtained for triple-therapy treatment with docetaxel, carboplatin, and anthracycline-epirubicin [ 48]. The combination of a taxane, such as paclitaxel or docetaxel, with cisplatin or carboplatin is a standard therapy for ovarian cancer. However, in this dual therapy, carboplatin is used more often, as it has relatively fewer side effects with the same level of effectiveness. The application of cabazitaxel and its efficacy and safety when used in combination with prednisone in the treatment of metastatic castration-resistant prostate cancer (mCRPC) was demonstrated by Tsao et al. (2014) [ 49]. Cabazitaxel exhibited a significantly lower IC ₅₀ value than docetaxel. The authors suggested that a combination of taxanes with pigment epithelium-derived factor (PEDF) could serve as a novel strategy for castration-resistant prostate cancer (CRPC) chemotherapy [ 50]. Taxanes are effective drugs that are used to treat many cancers. However, like other anticancer drugs, they have side effects. The main problem is the development of cardiotoxicity, especially when they are given together with doxorubicin. However, this applies not only to the cardiac muscle, but also to other organs, like the kidneys, liver, and brain. It was shown that docetaxel induces oxidative stress in blood plasma in rats bearing mammary tumours [ 51, 52]. Additionally, paclitaxel and docetaxel also generate oxidative stress in rat livers and brains [ 53, 54].

5. Camptothecin

Camptothecin (9) and its derivatives () belong to the pentacyclic group of quinoline alkaloids; these are isolated from Camptotheca acuminata and possess anticancer properties [ 17]. Camptothecin is present in the cortex, wood, and fruit of the Camptotheca acuminata plant. Camptothecin and its derivatives have also been obtained using different methods of synthesis [ 55, 56, 57, 58, 59]. The lactone rings of camptothecin are highly sensitive to hydrolysis which leads to the production of carboxylic acid derivatives (12) (). Hydrolysis leads to a loss of the antitumour activity of camptothecin [ 60].

Another disadvantage of this compound, as in the case of taxanes, is its poor solubility in water; however, its water-soluble semisynthetic derivatives, irinotecan (10) and topotecan (11), have found clinical application. The problem of hydrolysis in the camptothecin derivatives was solved by introducing a methylene group into their α-hydroxylactone ring, forming a stable, seven-membered ring in the structure (e.g., in diflomotecan) (13) which is not sensitive to hydrolysis ().

Another way to stabilise the α-hydroxylactone E-ring is to replace the lactone ring with a five-membered keto analogue of the ring. Such derivatives also retain high activity against topoisomerase I (TOP1) [ 61]. The derivative of camptothecin with a methylenedioxy ring and the substituent cyclobutane at position 7 demonstrates greater toxicity in different cancer cell lines than camptothecin (14) () [ 61, 62].

The antitumour activity of this group of drugs is a result of the formation of reversible DNA strand breaks in the normal cell cycle. Camptothecin binds to a complex consisting of DNA and topoisomerase I, thus preventing the reassembly of the DNA strands of a single chain [ 63, 64] (). At that time, camptothecin intercalates between the nitrogenous bases in the DNA strands.

The combining of the camptothecin drug with the DNA-topoisomerase complex prevents the restoration of the bonds at the sites of nicks and damages the structure of the double DNA chains. The double-strand breaks introduced by the replication process are probably the main reason for the DNA damage in the tumour cells that are treated with camptothecin and its derivatives, which are the drugs that specifically act on the S phase of the cell cycle. Another derivative of camptothecin is the hexacyclic exatecan (15), which has a 6-membered ring at positions 7 and 9, a methyl group at position 10, and a fluorine atom at position 11 ().

It was reported that the water-soluble exatecan is more effective as an anticancer drug than topotecan [ 65]. Currently, several derivatives of camptothecin are known, and only a few of them are discussed in this paper. Recently, Liu et al. (2015) [ 66] presented 187 novel camptothecin derivatives, several of which are characterised by high toxicity in relation to human tumour cell lines, such as lung carcinoma (A-549), prostate carcinoma (DU-145), nasopharyngea (KB), and vincristine-resistant nasopharyngea (KB-Vin). A camptothecin derivative, topotecan, is used in the first-line and second-line treatments as a chemotherapeutic agent for metastatic and small-cell lung cancers [ 67, 68]. In the European Union and the USA, it was accepted as the only drug in the second-line chemotherapy for recurrent small-cell lung cancer (SCLC). Irinotecan is used in the chemotherapy of gastrointestinal cancers [ 69, 70, 71]. This drug, in combination with 5-fluorouracil and leucovorin, is used as a chemotherapy for metastatic colorectal cancer [ 72]. In the first-line and second-line treatments of this cancer, combinations of bevacizumab and irinotecan have also been used [ 73]. Both of those camptothecin derivatives are used in the treatment of cervical cancer, gliomas, and sarcomas such as Ewing's sarcoma and rhabdomyosarcoma [ 74, 75]. In addition, both of those camptothecin derivatives have been used in clinical trials in the following cases: small-cell and non-small cell lung, breast, and hepatocellular carcinomas; mesotheliomas of the ovaries, cervix, oesophagus, stomach, pancreas, and kidney; and malignant neoplasms of the head and neck. Irinotecan and cisplatin have been used in the treatment of SCLC or extensive-stage SCLC [ 76]. Irinotecan is also used in the first-line and second-line treatments in combination with gemcitabine, cisplatin, and docetaxel in patients with metastatic pancreatic cancer [ 77, 78]. Higher toxicity was observed when exatecan was used with gemcitabine, compared to the use of gemcitabine alone. The combination of these two drugs was, however, not superior to the use of gemcitabine alone in the first-line treatment of advanced pancreatic cancer, in terms of the overall survival [ 79]. Certain other researchers have used irinotecan in combination with gemcitabine and celecoxib in the treatment of patients with advanced pancreatic cancer [ 80]. Gemcitabine has been used, either alone or in combination with irinotecan, leucovorin, and 5-fluorouracil, in the first-line treatment of the patients with metastatic pancreatic adenocarcinoma [ 81].

6. Combretastatin

Combretastatin (16) is a stilbene derivative that is present in the Combretum caffrum tree, also known as the "African willow", which grows in the Southeastern region of Africa. As a stilbene derivative, it may exist in trans (e.g., combretastatin A-1 (CA-1)) and cis (e.g., combretastatin A-4 (CA-4)) forms ().

Combretastatin A-4 and its derivatives were synthesized by Pettit and colleagues in 1987 [ 82]. Recently, the synthesis of new derivatives of podophylotoxins was performed and these were tested on skin carcinoma A431, human cervix adenocarcinoma HeLa, breast cancer cell lines: MCF7, MDA-MB-231, lung carcinoma A549, and ovarian cancer cells SKOV. These compounds efficiently inhibit tubulin polymerization with IC ₅₀ values below 1 μM [ 83]. Combretastatins are microtubule-targeting drugs similar to taxanes and vinca alkaloids. These compounds belong to the class of vascular disrupting agents (VDAs), which inhibit the angiogenesis of the tumour blood vessels. The mechanism of action of combretastatin as an antineoplastic compound is associated with its binding to β-tubulin at what is known as the colchicine site, causing the destabilisation of the microtubules. Inhibition of the tubulin polymerisation prevents the cancer cells from producing microtubules, which leads to the inhibition of cell proliferation, resulting in the process of apoptosis and/or the cytotoxic mechanism of action. While the combretastatin A-4 isomer is more potent as a tubulin binder, the combretastatin A-1 trans isomer exhibits a stronger cytotoxic effect. The molecules that have an amino group at position 2 either in ring A or ring B and a hydroxyl group at the 3' position are highly active [ 84]. On the other hand, the presence of a hydroxyl or methoxy group at the 4' position also provides cytotoxic ability. It has been demonstrated that combretastatin A4 inhibits proliferation, migration, and invasion, and promotes apoptosis in the human thyroid papillary carcinoma cell line (TPC1) [ 85]. A single intraperitoneal (i.p.) dose of combretastatin A4 resulted in 30% volume destruction (average) of the metastatic mass in liver metastasis within 24 h of the administration of the drug [ 86]. Combretastatins are also used in combination with other anticancer compounds in the treatment of anaplastic thyroid cancer (ATC). Combretastatin A-4 phosphate (CA4P) has been used in a series of combinations, first with paclitaxel and manumycin A (a selective farnesyltransferase inhibitor) and the second with paclitaxel and carboplatin. Both drug combinations were used in the treatment of ATC, which is extremely aggressive and has no effective available treatment to date. It was demonstrated that both triple-drug combinations exhibited excellent antineoplastic activity against anaplastic thyroid cancer [ 87]. The addition of CA4P to the combination therapy with paclitaxel and carboplatin was well-tolerated and led to a higher response rate in this patient population in comparison to chemotherapy without the addition of CA4P [ 88].

7. Podophyllotoxin

Podophyllotoxin (PPT) (19) is a toxin lignan isolated from the Berberidaceae family (i.e., Podophyllum). The resin known as podophyllin was obtained from the Podophyllum peltatum species found in North America. PPT was extracted from Podophyllum emodi resin from Asia [ 89]. Podophyllotoxin also occurs in the plants of the Linum amd Juniperus species and in Podophyllum versipelle [ 90]. Podophyllum peltatum plants also contain α-peltatin (17), β-peltatin (18) (), and their corresponding glycosides, along with podophyllotoxin-α-d-glucoside. The first synthesis of podophyllotoxin was performed by Gensler and Gatsonis in 1962.

Podophyllotoxin and its derivatives are aryl tetralin lactone (condensed tetracyclic ring with an aryl substituent) compounds that contain the lactone ring in its trans conformation. PPT and its derivatives exhibit significant biological activity as antiviral agents and as antineoplastic drugs. Podophyllotoxin and its glycosides exhibit a very strong cytostatic effect, as they disrupt the organisation of the karyokinetic spindle. These compounds attach to the colchicine domain of tubulin and inhibit tubulin polymerisation. In addition, the podophyllotoxins cause single-strand and double-strand breaks in DNA through their interactions with DNA topoisomerase II, inducing cell-cycle arrest in the G2-phase of the cell cycle. This activity is mediated through the formation of a stable complex with DNA and topoisomerase II. Etoposide (20) and teniposide (21) are the semisynthetic derivatives of podophyllotoxin and exhibit cytostatic activity ().

In contrast to podophyllotoxin, etoposide and teniposide do not inhibit the tubulin polymerisation; instead, they belong to the group of phase-specific drugs (work in interphase) [ 91]. In primary brain tumour cases, including paediatric patients with refractory or relapsed brain tumours, as a salvage treatment, the majority of the patients receive etoposide as a part of a multi-agent regimen that includes cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide [ 92, 93]. Etoposide and teniposide stabilise the intermediate covalent complexes formed between topoisomerase II and the cleaved DNA as well as the induction of DNA damage, which arrests the cell cycle in metaphase and leads to apoptotic processes [ 94, 95]. Podophyllotoxin is also used for the semisynthesis of anticancer drugs, such as etoposide, tenioposide, azatoxin, and etopophos as well as NK611, GL331, TOP-53, and tafluposide [ 94, 96]. PPT derivatives are used in the treatment of numerous cancers, such as lymphomas, neuroblastomas, sarcomas, testicular and ovarian cancers, brain tumours, gastrointestinal cancer, cervical carcinomas, osteosarcomas, nasopharyngeal carcinomas, colon cancer, breast cancer, prostate cancer, small-cell lung cancer, and testicular carcinomas [ 97]. Podophyllotoxin is a highly toxic compound, and therefore, it is rarely used in cancer therapy [ 94]. In contrast, its derivatives, such as etoposide and teniposide, are used in therapy for lung cancer, testicular cancer, lymphomas, and gliomas [ 91]. PPT derivatives are also used in the combination therapy, for example, in combination with cisplatin in the first-line chemotherapy for small-cell lung cancer or extensive-stage SCLC [ 75]. However, in certain studies that have been conducted on the effectiveness of chemotherapy in the treatment of small-cell lung cancer, a combination therapy with cisplatin, etoposide and irinotecan drugs was compared to the topotecan monotherapy. It was demonstrated that the combination chemotherapy could serve as the standard second-line chemotherapy in the sensitive recurrent SCLC [ 98]. Moreover, podophyllotoxin also exhibits anti-multidrug resistance (anti-MDR) potential against a variety of drug-resistant tumour cells. Recently, 766 novel derivatives of podophyllotoxin have been reported. Several of these have been tested on the cancer cell lines, where they exhibited high anticancer activity and are very much expected to be tested as anticancer drugs in the undergoing clinical trials [ 99]. Recently, Zhang et al. (2017) [ 97] demonstrated that 76 novel derivatives of podophyllotoxin exhibit biological activity, including the anticancer properties. Deoxypodophyllotoxin (DPT), which is closely related to podophyllotoxin structurally (lack of hydroxyl group in ring C), is a potent antitumour and anti-inflammatory agent. DPT is isolated from Juniperus communis (common Juniper) as aryltetralin lignan deoxypodophyllotoxin as potent inducers of apoptosis in malignant MB231 breast cancer cells [ 100].

8. Geniposide and their derivatives

Geniposide (GS) occurs in nearly 40 species belonging to different families; however, the most famous sources of geniposide are the fruits of Gardenia jasminoides Ellis (Rubiaceae), which have been used in Chinese medicine for centuries. Numerous other species of this genus and the other members of the Rubiaceae family are known to contain the geniposide. Currently, about 90 different derivatives of the geniposide backbone are known. Genipin (22) is an aglycone that is formed by the hydrolysis of geniposide (23) which occurs in the same plant material along with the other derivatives, such as geniposidic acid (24) () [ 101]. Other biologically active iridoid derivatives was described by Liu and Lou in 2007 [ 102].

Other derivatives based on the iridoid backbone are most often the glycosides or esters of aromatic acids. It has been demonstrated that genipin and geniposide exhibit antidiabetic effect, as well as neuroprotective effects in neurodegenerative diseases (e.g., Alzheimer's disease) [ 103, 104]. The derivatives of iridoid glycoside geniposide are a relatively novel group of compounds with antitumour activity, which have been recently submitted to a critical review. The work discussed the influence of this group of compounds on the development of tumour cells and their mechanisms leading to the death of cancer cells. The work also discussed the pro-oxidant and antioxidant mechanisms of these compounds, the generation of reactive oxygen species, cell-cycle regulation, and the pro-inflammatory properties of these compounds [ 105, 106]. Geniposide has been reported to inhibit the hydroperoxide and myeloperoxidase formation caused by 12-O-tetradecanaoylphorbol-13-acetate (TPA) in addition to inhibiting TPA-induced skin tumours in female CD-1 mice in vivo [ 107]. It has reported that genipin exhibits a strong apoptotic cell death effect in human non-small-cell lung cancer H1299 cells. Genipin caused increased levels of Bax in response to p38MAPK signaling, which led to the initiation of the mitochondrial death cascade [ 108]. Recently, the properties of geniposide and its derivatives as well as their toxicology and pharmacology have been described [ 101].

9. Colchicine

Colchicine (25) () is an alkaloid that is extracted from the plants of the Colchicum genus (e.g., the autumn crocus, Colchicum autumnale, also known as "meadow saffron"). Colchicine was synthesized for the first time by Van Tramalen and collaborators (1959) [ 109].

Similar to vinca alkaloids, the mechanism of action of colchicine is based on the depolymerisation of the microtubules at high concentrations and the stabilisation of the microtubule dynamics at low concentrations. Most of the antimitotic drugs, such as podophyllotoxin and combretastatin, bind to the colchicine domain of tubulin and interfere with the in vitro and in vivo assembly of the microtubules in the lowest-possible effective concentrations that stabilise the microtubule dynamics. Colchicine may modify the voltage-dependent anion channels of the mitochondrial membrane and increase the cellular free tubulin to limit mitochondrial metabolism in the cancer cells [ 110]. Colchicine is a highly toxic and very cheap alkaloid and has been used in medicine for a long time. For example, the antiproliferative effect of colchicine on hepatocellular carcinoma cells is approximately 200-fold less than that of epirubicin. It has been demonstrated that a low colchicine concentration is clinically acceptable in the palliative treatment of hepatocellular carcinoma [ 111] and cholangiocarcinoma [ 112]. The inhibition effect of 6 ng/mL colchicine on the growth of hepatocellular carcinoma cells was shown to be equivalent to the effect of 1 mg/mL epirubicin, which is the maximum plasma concentration of this drug used in patients. It has been demonstrated that colchicine exhibits inhibitory effects on the proliferation of two human gastric cancer cell lines (AGS and NCI-N87). Colchicine has also been demonstrated to inhibit tumour growth in nude mice [ 113]. In patients with gout who were treated with colchicine, the incidence of all-cause cancers was significantly lower in comparison to patients who did not receive the colchicine treatment [ 114]. Similar to the vinca alkaloids, colchicine also depolymerises the microtubules when it is used at high concentrations and stabilises the microtubule dynamics when used at low concentrations. Colchicine inhibits the microtubule polymerisation by binding to the microtubule ends, rather than binding to the soluble tubulin pool. However, the free colchicine itself probably does not bind directly to the microtubule ends. Instead, it first binds to the soluble tubulin, which induces gradual conformational changes in the tubulin and ultimately, forms a poorly reversible tubulin-colchicine complex, which then copolymerises into the microtubule ends in small numbers along with numerous free tubulin molecules [ 112].

10. Artesunate

Artesunate (26) () is a semi-synthetic derivative of artemisinin isolated from a Chinese plant Artemisia annua L. medicinal (Asteraceae) [ 5]. Artemisinin was synthesized by Yadav and co-workers (2003) [ 115]. It was used as an antimalarial drug. It has been shown that artesunate exhibits activity against certain types of cancer through an anti-angiogenic mechanism. Artemisinin and its derivatives inhibit the growth and proliferation of cells and selectively kill tumour cells. Recently, many new artemisinin derivatives have been described, and it is possible that many of them will be effective against cancer [ 116].

It also demonstrated activity against chronic leukaemia in vitro and in vivo. It has been indicated that these compounds have low toxicity and are promising agents in antileukemia chemotherapy [ 117]. Additionally, artemisinin is not transported with P-glycoprotein, so it is not involved in multidrug resistance [ 118]. After the administration of artemisinin to rats for several weeks, severe adverse effects were not found [ 119]. Other studies compared the efficacy and toxicity of artesunate combined with vinorelbine and cisplatin, as well as artesunate alone, in the treatment of advanced non-small cell lung cancer (NSCLC). Artesunate combined with vinorelbine and cisplatin can elevate the short-term survival rate and prolong the mean survival time of patients, without extra side effects [ 120]. Zhao et al. (2013) [ 121] reported that artemisinin is cytotoxic to retinoblastoma cell lines with low cytotoxicity on normal retina cell lines. Artemisinin therapy has also been used in clinical trial studies without serious adverse effects [ 122]. Artemisinin was also combined with daunorubicin to produce overall antitumour efficacy without signs of toxicity in mice [ 123]. No adverse effects have been observed in the treatment of breast cancer either [ 124]. Artesunate exhibited antitumour activity against human pancreatic cancer through the induction of apoptosis. This effect depended on the stage of differentiation and was more effective against less diverse cells. Additionally, it enhanced the effects of gemcitabine in the control of pancreatic cancer [ 125]. Artesunate was reported to be effective against chemoresistant neuroblastoma cells. This drug was shown to induce apoptosis and reactive oxygen species in neuroblastoma cells [ 126].

11. Homoharrigtonine

Another anticancer drug is homoharrigtonine (Omacetaxine mepesuccinate) (27) (), which was first isolated in 1963 from several Cephalotaxus (Cephalotaxaceae), including C. harringtonia K. Koch, and C. haianensis qinensis, all of which are used in traditional Chinese medicine. The first synthesis of homorringtonine was performed by Hiranuma and Chudlicky (1982) [ 127]. These compounds were used in the treatment of various types of cancer, particularly in leukaemia and breast cancer. The action of these drugs is connected with the block of synthesis in the peptidyl transferase centre and leads to cell apoptosis [ 128]. The use of homoherringtonin in chronic myeloid leukaemia made it possible to achieve remission in 92% of patients, with a favourable cytogenetic response in 68%. Current research is aimed at increasing the therapeutic effect by combining homoharringtonine with IFN-α and cytarabine in low doses in patients with worse prognoses [ 129].

12. Salvicine

Salvicine (28) () is a modified diterpenoquinone derivative isolated from the Chinese herb Salvia pronitis Hance (Labiatae). Salvicine was chemical synthesized by Sheng et al. in 1999 and it has shond potent inhibitory activity against a wide spectrum of human tumour cells in vitro and in mice bearing human tumour xenografts [ 130]. Salvicine and its derivatives are nonintercalative topoisomerase II poisons that exhibit strong antitumour effects in vitro and in vivo and a broad spectrum of anti-multidrug resistant activity [ 131]. Salvicine initiates the break of two strands of DNA by facilitating TOP2 activity, inhibiting re-ligation, which is associated with the inhibition of tumour growth. In human cancer cells, salvicine induces damage to specific DNA genes, leading to apoptosis. Additionally, reactive oxygen species have been shown to play a key role in the salvicine-induced cellular response, including TOP2 inhibition, DNA damage, circumventing MDR and tumour cell adhesion inhibition [ 130]. It was reported that new series of salvicine derivatives demonstrated potent cytotoxicity against tumour cell lines [ 132].

13. Elipticine

The ellipticine (5,11-dimethyl-6H-pyrido-(4,3-b)-carbazole) (29) () is an alkaloid found in Apocyanaceae species. It was isolated from the leaves of Ochrosia elliptica Labill. Synthetic ellipticine was obtained by Woodward et al. (1959) [ 133], and together with its more soluble derivatives, it exhibits considerable antitumoural activity.

Ellipticins bind strongly to DNA, forming covalent bonds, and/or to TOP2 [ 134] and lead to disruption of the cell cycle by regulating the expression of some kinases, such as cyclin B1 and Cdc2 [ 135]. In addition, they can phosphorylate the latter cyclin, inducing apoptosis and generation of cytotoxic free radicals [ 136]. Ellipticine is also an inhibitor or inducer of biotransformation enzymes. Through modulation, this metabolism indicates genotoxic and pharmacological effects. Ellipticine is cytotoxic in human breast cancer cells (MCF-7), leukemia (HL-60 and CCRF-CEM) cells, neuroblastoma (IMR-32, UKF-NB-3 and UKF-NB-4) cells, and glioblastoma cells (U87MG) [ 137]. Its powerful antitumour activity, e.g., pharmacological efficiency and/or genotoxic side effects, are dependent on its cytochrome P450 (CYP)- and/or peroxidase-mediated activation to species forming covalent DNA adducts [ 138]. In clinical trials, ellipticine has been observed to induce the remission of tumour growth.

14. Roscovitine

The next anticancer compound is a purine-based, semisynthetic derivative of R-roscovitine (30) (), which is derived from olomoucine and was isolated from the cotyledons of Raphanus sativus L. (Brassicaceae).

Roscovitine was synthesized by Meijer et al. (1997) [ 139] and is one of the most promising members of the cyclin-dependent kinase (CDK)-inhibitor family. It has been shown that roscovitine, a potent CDK/cyclin E inhibitor, exhibits a wide spectrum of actions against cancer, neurodegenerative diseases, viral infections, and glomerulonephritis. Roscovitine was used in phase-2 clinical testing against lung and breast cancer, and phase-1 clinical trials against glomerulonephritis. Seliciclib has been shown to inhibit RNA-polymerase-II dependent transcription and down-regulation of the protein MCL1 [ 140]. Olomoucine is a cyclin-dependent kinase inhibitor (CDK4) [ 141]. In turn, roscovitine specifically inhibits CDK5 activity with concomitant inhibition of MDA-MB231 cell proliferation and induction of apoptosis. In contrast, olomoucine does not affect MDA-MB231 cell proliferation and apoptosis; however, roscovitine-mediated inhibition of proliferation is irreversible [ 142]. These data suggest that CDK5 may have a significant role in the regulation of breast cancer cell proliferation and apoptosis. However, roscovitine has a stronger effect on it than olomoucine [ 62]. The probable mechanism of action of roscovicine and its derivatives is related to the inhibition of cyclin-dependent kinase activity, which preferentially inhibits numerous target enzymes, such as CDK1, CDK2 and CDK5, leading to cell-cycle arrest in the G1 and G2 phases [ 142, 143]. It was reported that roscovitine inhibits RNA synthesis in human cells, probably by mechanisms other than CDK inhibition [ 144]. A synergistic mechanism of action of roscovitine with the farnesyltransferase inhibitor during the induction of apoptosis in HL-60 cells was reported, since similar synergy was observed with a leukemic cell line (CEM) and a prostate cancer cell line (LNCaP) [ 144, 145]. Wortmannin, a phosphatidylinositol-3-kinase (PI3K) inhibitor, was shown to enhance the effects of roscovitine by causing a reduction in the mitochondrial transmembrane potential, increasing cytochrome c release and activating caspase-3, as well as enhancing the activation of Bax and Bad [ 143]. These results suggest that roscovitine inhibits Ang II-induced angiotensinogen expression by hindering the activation of ERK1/2 and c-Jun [ 146]. Roscovitine was shown to exert clear dose-dependent anti-proliferative and pro-apoptotic effects in glioblastoma A172 [ 147]. It was reported that roscovitine has a synergistic effect with other anticancer drugs, such as doxorubicin, paclitaxel, 5-fluorouracil, vinblastine, alemtuzumab, trastuzumab, cisplatin, irinotecan, etoposide, and tamoxifen, as well as with radiation [ 148].

15. Maytansin

Maytansin or maytansine (31) () is a cytotoxic agent that was isolated in 1970s from the Ethiopian plant Maytenus serrata (Celastraceae) or Maytenus ovatus and it was synthesized by Corey and co-workers (1980) [ 149]. Maytansin and its derivatives belong to the natural product group of maytansinoids, which have antimitotic effects that are attributed to their ability to inhibit microtubule assembly by binding to tubulin near the vinblastine binding site [ 150].

The mechanism of action of maytanasin is the same mechanism as in the vinca alkaloids. Maytansin was used as an effective drug (in vivo) against Lewis lung carcinoma and B16 murine melanocarcinoma solid tumours and has antileukemic activity against P388 murine lymphocytic leukaemia. The maytansinoids belong to the ansamycin group of natural products containing ansamacrolide structures attached to a chlorinated benzene ring. Many maytanasin derivatives were synthesized by Cassidy et al. (2004) [ 151]. Although maytansin is cytotoxic to cancer cells, its clinical application has been hampered by severe side effects and poor efficacy [ 151]. However, its derivatives, especially maytansin analogues conjugated to antibodies (maytanosoids), are used in various types of cancer chemotherapy [ 152, 153]. However, maytansinoids were shown to be 20 to 100 times more potent than vincristine in vitro [ 154]. The mechanism of action of maytansinoids is related to their high affinity to receptors expressed on the surfaces of cancer cells. The HuN901 monoclonal antibody conjugate with maytansin showed high affinity for CD56 [ 155]. This drug has been used with good efficiency in primary multiple myeloma (MM) cells showing the expression of CD56. Another maytansinoid conjugate, trastuzumab-DM1, yielded promising results in patients with metastatic breast cancer during a phase II clinical trial [ 153].

16. Thapsigargin

Thapsigargin (TG) (32) () is a lactonic sesquiterpene that was isolated from the roots of Thapsia garganica L. (Apiaceae) collected from Ibiza island [ 142]. Thapsigargin, which was synthesized by Ball et al. (2007) [ 156], and its derivative represent a group of antineoplastic drugs. Thapsigargin is an inhibitor of sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) in the sarco/endoplasmic reticulum. Thapsigargin leads to an increase in the intracellular calcium concentration by blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticulums [ 157].

Thapsigargin induces perturbations in calcium homeostasis and an increase in nitric oxide concentration induces apoptosis and cell death [ 158]. A disturbance in calcium concentration enhances endoplasmic reticulum stress, which, in turn, leads to caspase activation, the release of apoptotic factors from the mitochondria, and direct activation of calcium-dependent endonucleases that cleave cellular DNA, resulting in cell death [ 159, 160]. Thapsigargin specifically inhibits the fusion of autophagosomes with lysosomes, the last step in the autophagic process leading to cellular death [ 161]. Thapsigargin is useful in experiments examining the impacts of increasing cytosolic calcium concentrations. TG has been shown to induce apoptosis in quiescent and proliferating prostate cancer cells where standard anti-proliferative chemotherapy is ineffective, although it did not show selectivity for those cells. In clinical studies, it was shown to be associated with a carrier peptide to produce a prodrug activated by prostate-specific membrane antigen (PSMA). Mipsagargin is a novel derivative of thapsigargin-based targeted prodrug, which is activated by PSMA-mediated cleavage of an inert masking peptide. Similar to TG, it is an inhibitor of the calcium adenosine triphosphatase (SERCA) pump protein that is necessary for cellular viability. Mipsagargin was used in patients with advanced solid tumours and established a recommended phase II dosing (RP2D) regimen. It was found to have an acceptable tolerability and favourable pharmacokinetic profile in patients with solid tumours [ 162].

17. Bruceantin

Bruceantin (33) () was first isolated from Brucea antidysenterica (Simaroubaceae), a tree that grows in Ethiopia, which is used by the local population in the treatment of "cancer" [ 142].

Brucantin was synthesized by Sasaki and Murae (1989) [ 163]. The anticancer activity of bruceantin has been observed in the treatment of various cancers, such as B16 melanoma, colon 38, and L1210 and P388 leukaemia, in mice. The activity of bruceantin has been studied with several leukaemia, lymphoma, and myeloma cell lines. However, no objective tumour regressions were observed in clinical development in phase I and II clinical trials, so application of this drug was terminated. On the other hand, resumed research exhibited the activity of bruceantin against leukaemia, lymphoma, and myeloma cell lines in animal models with advanced stages of the disease. It was demonstrated that treatment of HL-60 and RPMI 8226 cell lines induced apoptosis, and this involved the caspase and mitochondrial pathways. Moreover, an in vivo study using RPMI 8226 human-SCID xenografts revealed that bruceantin induced regression in early as well as advanced tumours. The main mechanism of bruceantin action associated with anticancer activity is the inhibition of protein synthesis through interaction with peptidyltransferase, which blocks the formation of peptide binding [ 164]. It was demonstrated that the alcohol extract of the fruit of Brucea javanica (Fructus Bruceae) possesses significant cytotoxicity in pancreatic adenocarcinoma cell lines. Seven quassinoids were identified after their fractionation and purification, including brusatol, bruceine D, bruceine H, yadanzioside A, yadanzioside G, javanicoside C, and bruceantinoside A. Brusatol exhibited the most potent in vitro antipancreatic cancer action on PANC- 1 and SW1990 cell lines [ 165].

18. Marine Natural Compounds

18.1. Psammaplin

Psammaplin A (PsA) (34) is an anticancer compound isolated from Poecillastra sp. and Jaspis sp. It was first isolated from Psammaplin aplysilla sea sponges [ 169]. PsA and biprasin are present in marine microalgae, cyanobacteria, and in the heterotrophic bacteria living in association with invertebrates (e.g., sponges, tunicates, and soft corals). Psammaplin A is a phenolic compound containing a disulphide bridge; it occurs in nature in the form of monomers or dimers. Additionally, psammaplin A contains a bromotyrosine ring. PsA exhibits varying effects on different pathways. Psammaplin A was synthesized by Hoshino and co-workers (1992) [ 170]. This drug exhibits antitumour properties and inhibits aminopeptidase N, which is a key factor in tumour cell invasion and angiogenesis [ 171]. Psammaplin A has been demonstrated to inhibit the proliferation of leukaemia cells through the induction of apoptosis, as well as the cell growth of Bap1-null cells, while causing minimal toxicity to human neuroblastomal SKN cells [ 172, 173]. The results obtained are particularly strong when this drug is used in combination with camptothecin (a DNA damage inducing drug). This indicates that psammaplin A could serve as a potential adjuvant therapy for the cancer patients, particularly for Bap1-null lung cancer patients who are treated with the DNA damage-inducing therapies [ 173]. Psammaplin A (34) and its derivatives, psammaplin F (35), psammaplin G (36), and biprasin (37) (), inhibit histone deacetylase (HDAC) activity, which performs a key role in tumourigenesis and angiogenesis.

Psammaplin A also inhibits various enzymes, including topoisomerase II, farnesyl-protein transferase, leucine aminopeptidase, and chitinase [ 174]. Additionally, this compound causes cell-cycle arrest and the induction of apoptosis in numerous human cancer cells. PsA has demonstrated antiproliferative activity and induces cell cycle arrest or apoptosis in Ishikawa human endometrial cancer cells [ 175]. Furthermore, psammaplin F is a selective histone deacetylase inhibitor, while psammaplin G is a selective DNA methyltransferase inhibitor. NVP-LAQ824 (38) () is a synthetic derivative of indol and a strong histone deacetylase inhibitor that is used in the treatment of solid and haematological malignancies. NVP-LAQ824 exhibits antileukaemic activity when administered in the low nanomolar range. It has also been used in clinical trials in patients with solid tumours or leukaemia. NVP-LAQ824 demonstrated low host cell toxicity in HCT116 colon cancer and A549 human lung cancer xenografts; also, it caused apoptosis in the A549 lung cancer cell line and the normal human fibroblast cell line [ 176].

18.2. Didemnin B

Didemnin B ( 39) is a cyclic depsipeptide which was isolated from the marine tunicate Trididemnum solidum. It was the first marine natural compound to enter clinical trials as an antitumour agent. It exhibits structural similarity to the cyanobacterial metabolites [ 177]. Didemnin B was synthesized by Ramanjulu and co-workers (1997) [ 178]. In clinical trials, it exhibited anticancer activity against a variety of tumours, such as bronchial carcinoid, colon cancer, oesophageal cancer, malignant melanoma, medullar thyroid carcinoma (MTC), metastatic breast cancer, non-small cell lung cancer, renal cancer, and squamous cell cervical cancer [ 179]. Didemnin B inhibits the synthesis of ribonucleic acid (RNA), DNA, and proteins and binds non-competitively to palmitoyl-protein thioesterase [ 180]. It has been demonstrated that didemnin B is able to induce apoptosis in a wide range of transformed cell lines. Didemnin B was shown to induce apoptosis in normal lymphocytes only after mitogenic stimulation [ 181]. The use of this drug in leukaemia requires further research. Furthermore, rapamycin inhibits didemnin-induced apoptosis in human HL60 cells, suggesting the activation of the FK506-binding protein apoptotic pathway [ 182]. Didemnin B () possibly modulates the activity of FK506-binding proteins as a part of its immunomodulatory process, and thus leads to cell death via apoptosis. Plitidepsin (aplidine) (40) is an anticancer agent obtained from the ascidian Aplidium albicans. It binds specifically to the alpha subunit of the eukaryotic Elongation Factor 1 (eEF1A2), resulting in tumour cell death via apoptosis.

eEF1A2 is overexpressed in human tumours, favouring tumour cell proliferation and inhibiting apoptosis. Previous experiments have demonstrated that plitidepsin localises in tumour cells that are sufficiently close to the eEF1A2, indicating the formation of drug-protein complexes in the living cells [ 183]. Plitidepsin also interferes with the synthesis of DNA and proteins and induces cell cycle arrest in the G1 and G2 phases of the cell cycle [ 184]. This compound is currently under clinical development for haematological cancers, including a phase Ib trial of a triple-drug combination of plitidepsin, bortezomib, and dexamethasone for relapsed or refractory multiple myeloma and a phase II study for relapsed or refractory angioimmunoblastic T-cell lymphoma. In a study assessing the clinical benefit of plitidepsin in patients with advanced medullary thyroid carcinoma (MTC), plitidepsin appeared to be able to induce clinical benefits in patients with pretreated MTC, and its toxicity was manageable at the recommended dose [ 185]. Additionally, aplidine appears to work more selectively against leukaemia and lymphoma cells than against normal cells. Furthermore, the activity of aplidine has been observed to be independent of the other anticancer drugs that are commonly used in the treatment of leukaemia and lymphoma, suggesting that aplidine may be effective in cases which have proven unresponsive to the other anticancer agents/drugs [ 186].

18.3. Dolastatin

Dolastatin 10 ( 41) () was first isolated in 1972 from the sea hare Dolabella auricularia. However, the performance of this drug was very low due to its low concentration. Significantly higher yields were obtained from the marine cyanobacteria Symploca hydnoides and Lyngbya majuscule which were also synthezised by Tomioka and coworkers (1991) [ 187].

Dolastatin 10 is a pentapeptide with four of its amino acid residues being structurally unique (dolavaline, dolaisoleucine, dolaproline, and dolaphenine, in addition to valine). This compound has demonstrated pronounced antineoplastic activity. Interestingly, at the time of its discovery, it was referred to as the most potent antiproliferative agent. The semisynthetic/synthetic derivatives of dolastatin, such as auristatin PE (TZT-1027, soblidotin) ( 42), synthadotin (ILX651) ( 43), and cematodin (LU-103793) ( 44), which usually possess improved pharmacological and pharmacokinetic properties [ 188, 189]. The antitumour activity of TZT-1027 (soblidotin), a synthetic derivative of dolastatin 10, was observed to be superior to that of the existing anticancer drugs, such as paclitaxel and vincristine; TZT-1027 is currently undergoing phase I trials for the treatment of solid tumours [ 189]. The third-generation dolastatin 15 ( 45) derivative, synthadotin (ILX-651, tasidotin), is another antitumour agent that is currently undergoing phase II trials after its successful use in the phase I trials [ 188, 190]. Dolastatin 10 has been used in trials for the treatment of sarcoma, leukaemia, lymphoma, liver cancer, kidney cancer, etc. Although dolastatin has not been directly used clinically for the treatment of moderate peripheral neuropathy in 40% of the patients, its derivatives, such as soblidotin and auristatin PE, were designed with the goal of maintaining the antitumour activity potential while reducing the toxicity of the parent compound [ 191]. Auristatin is the semisynthetic derivative of dolastatin 10; to produce this compound, the thiazole ring was removed from the original dolaphenine residue. The application of auristatin led to the inhibition of growth in the P388 leukaemia cells and the diminution of three solid-tumour cell lines (colon-26 adenocarcinoma, B16 melanoma, and M5076 sarcoma) with an efficacy equivalent to or greater than that of dolastatin 10 [ 176]. Furthermore, TZT-1027 was shown to be effective in two human xenograph models-breast carcinoma MX-1 and lung carcinoma LX-1 [ 192]. Dolastatin 15, which was synthesized by Patino et al. (1992) [ 193], is a small linear depsipeptide compound which is considered a promising anticancer drug that exhibits potency against breast and liver cancers, solid tumours, and certain types of leukaemia. In contrast to dolastatin 10, dolastatin 15 binds directly to the vinca domain of tubulin, and its mechanism of action is similar to that of the vinca alkaloids. It inhibits the microtubule assembly by interfering with tubulin formation, thereby disrupting mitotic cell division and consequently, inducing apoptosis in cancer cells. Synthadotin (ILX651) is an orally-active, third-generation synthetic derivative of dolastatin 15 that contains a terminal tert-butyl moiety. Synthadotin has been used in three phase II clinical trials in patients with locally-advanced or metastatic non-small cell lung cancer, and in patients with hormone-refractory prostate cancer who have been treated previously with docetaxel [ 194, 195]. Synthadotin has also been demonstrated to be a well-tolerated drug for the treatment of patients with inoperable locally-advanced or metastatic melanoma [ 194].

18.4. Ecteinascidin

Ecteinascidin-743 (ET-743, Trabectedin) ( 46) is a tetrahydroisoquinoline alkaloid isolated from the Caribbean marine tunicate Ecteinascidia turbinata. This compound contains three fused tetrahydroisoquinoline rings. Trabectedin has previously been isolated from aquacultures and even produced synthetically, eventually leading to the semisynthesis of ET-743 ( 49) from cyanosafracin B ( 50). In turn, cyanosafracin B could be obtained from the fermentation of the marine bacterium Pseudomonas fluorescens [ 196] ().

Although less potent in vivo than its N-demethyl analogue (ET-729), trabectedin exhibits highly potent antitumour activity with a cytotoxicity (IC ₅₀) value of 0.5 ng/mL against the L1210 leukaemia cells [ 176]. Trabectedin interacts with DNA through the covalent interactions of two of its tetrahydroisoquinoline rings with the minor groove of the DNA double helix, while the third ring protrudes from the DNA duplex, apparently allowing interactions with the adjacent nuclear proteins [ 197, 198]. The interactions of trabectedin with DNA trigger a cascade of events that are associated with several transcription factors such as the DNA-binding proteins and with DNA-repair pathways, making this drug different from the other DNA-interacting agents. Additionally, this compound leads to modulation of the production of cytokines and chemokines by tumour and normal cells. It has been suggested that the anticancer activity of trabectedin could also be associated with changes in the tumour microenvironment [ 198]. Trabectedin treatment demonstrated the greatest response in advanced ovarian, breast, and mesenchymal tumours which had been pretreated heavily with platinum/taxane therapy. Phase II clinical trials of this drug were conducted for ovarian, endometrial, breast, prostate, and non-small cell lung cancers, with notable recent success in the combination drug therapy [ 195]. Promising combinations of trabectedin with other anticancer drugs were observed during preclinical studies. One of these combinations (trabectedin-PEGylated liposomal doxorubicin) was recently authorised by the European Commission for the treatment of patients with relapsed platinum-sensitive ovarian cancer [ 198].

18.5. Halichondrin B

Halichondrin B (48) is a complex polyether that is isolated from marine animals such as sponges and tunicates. Halichondrins were first isolated from the Japanese sponge Halichondria okadai by Uemura et al. (1985) [ 199], and their structures were determined using X-ray crystallography. Subsequently, halichondrin B and several of its natural analogues (49) () were isolated from various unrelated sponges, including the Lissodendoryx sp., Phakellia carteri, and Axinella sp. However, they may also be obtained from several other species, especially fish [ 172]. Halichondrin B, as well as palytoxin and maitotoxin, exhibit structural complexity and were synthesized by Aicher et al. (1991) [ 200]. Several studies have examined their mechanisms for cell toxicity, and it was discovered that the halichondrins are potent tubulin inhibitors that bind non-competitively to the vinca-binding site and cause a characteristic G2-M cell-cycle arrest through a concomitant disruption of the mitotic spindle. Exquisite anticancer activity of halichondrin B and homohalichondrin B against the murine cancer cells was reported in both culture and in vivo studies. These studies confirmed that both compounds are highly cytotoxic (IC ₅₀ values of 0.3 nM and 1 nM, respectively, against the L1210 murine leukaemia cells), causing the accumulation of cells arrested in mitosis at toxic concentrations. The studies also confirmed that both compounds inhibit the polymerisation of purified tubulin and microtubule assembly that is dependent on microtubule-associated proteins [ 201].

19. Conclusions

Modern chemotherapy utilises many substances of plant and aquatic origin. These compounds have cytotoxic properties with many different mechanisms of action, such as the inhibition of tumour cell growth, the induction of apoptosis, DNA damage, the inhibition of topoisomerases I and II, the induction of apoptosis, and others. Studies have shown that plant-derived compounds in combination with anticancer drugs have great potential to destroy tumour cells while not affecting normal cells such as lymphocytes and fibroblasts. Several of these substances are undergoing preclinical testing or are in the subsequent stages of clinical trials. Although these substances exhibit high potential for cancer treatment, they also exhibit several side effects. Certain substances are not suitable for use as drugs due to their high toxicity, although their synthetic/semisynthetic derivatives have been used as drugs in cancer treatment. The side effects of anticancer drugs may be reduced by using nanoparticle encapsulations to transport the drugs to their target sites. Drugs may also be administered in the form of liposomes, which serve as carriers for the drug. An additional argument associated with the nanoparticles is the limitation of multi-drug resistance. Although several compounds of plant origin are known to serve as anticancer drugs, modern medicine lacks effective drugs against certain types of cancers, for example, metastatic pancreatic adenocarcinoma and castration-resistant prostate cancer. The marine environment is characterized by a huge diversity of organisms, creating a wide range of opportunities for acquiring new substances with anticancer activity, which is a challenge for scientists involved in this research. We also need to improve techniques related to the isolation of substances from natural materials to obtain higher yields with concern for the environment. Considering the huge costs associated with the discovery and development of effective anticancer drugs, natural compounds can be an inexhaustible source here.

Abbreviations

Author Contributions

A.L. participated in the study design and in writing the manuscript, especially in proofreading; writing-review and editing; K.G. participated in the study design; wrote the manuscript and gave the final approval of the version to be published. Both authors read and approved the final manuscript.

Conflicts of Interest

The authors declare no conflict of interest. We confirm all figures and tables in your manuscript are non-published and original.

References

# data[].attributes.attachment_link.title
Anticancer Activity of Natural Compounds from Plant and Marine Environment

# data[].attributes.attachment_link.description
This paper describes the substances of plant and marine origin that have anticancer properties. The chemical structure of the molecules of these substances, their properties, mechanisms of action, their structure-activity relationships, along with their anticancer properties and their potential as chemotherapeutic drugs are discussed in this paper.

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WEEK 5 (N.N.Izzati, Rafiqah, Atiqa, Adilah, Haiffa)

# data[].attributes.subject
WEEK 5 (N.N.Izzati, Rafiqah, Atiqa, Adilah, Haiffa)

# data[].attributes.body
Modified Eremophilanes from Parasenecio hastatus and Their Neuroprotective Activities.

New compound that is modified from eremophilane

1)      Furanoeremophilane-type skeleton

2)      Rare C₁₄ nor-eremophilane-type skeleton

3)      Eremophilane lactone-type skeleton

Source and references:

Tingting Liu, Haibo Wu, Jing Zhang, Wenjie Deng, and Luowenlei Yang

Journal of Natural Products 2020 83 (2), 185-193

DOI: 10.1021/acs.jnatprod.9b00217

# data[].attributes.attachment_link.title
Modified Eremophilanes from Parasenecio hastatus and Their Neuroprotective Activities.

# data[].attributes.headline
Week 3 (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)

# data[].attributes.subject
Week 3 (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)

# data[].attributes.body
Isolation and Identification of the Five Novel Flavonoids from Genipa americana Leaves

Novel compounds being isolated:
1. quercetin-3-O-robinoside
2. kaempferol-3-O-robinoside
3. isorhamnetin-3-O-robinoside
4. kaempferol-3-O-robinoside-7-O-rhamnoside (robinin)
5. isorhamnetin-3-O-robinoside-7-rhamnoside

Source & Reference: https://www.mdpi.com/1420-3049/23/10/2521

# data[].attributes.body
OK, two groups submitted. We want more group to share the isolated components yeah!
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Anonymous
16d
OK, two groups submitted. We want more group to share the isolated components yeah!
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Week 3 (izzani, balqis, marsha, syafika, izzati) (k2)
Avatar of anonymous
Anonymous
15d
Week 3 (izzani, balqis, marsha, syafika, izzati) (k2)
The Alkaloids and Bioactivities of Ethanol Extract from a Traditional Remedy of Vietnam

compound names:
1) palmatine 
2) berberine


Source and reference :

http://www.eurekaselect.com/168727/article
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Week 3 (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)
Avatar of Aaron Yang
Aaron Yang
6d
Week 3 (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)
Isolation and Identification of the Five Novel Flavonoids from Genipa americana Leaves

Novel compounds being isolated:
1. quercetin-3-O-robinoside
2. kaempferol-3-O-robinoside
3. isorhamnetin-3-O-robinoside
4. kaempferol-3-O-robinoside-7-O-rhamnoside (robinin)
5. isorhamnetin-3-O-robinoside-7-rhamnoside

Source & Reference: https://www.mdpi.com/1420-3049/23/10/2521
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# data[].attributes.headline
Week 6 (Group Aaron, Vatsala, Jin Min, Jing Rou,CK) (K2)

# data[].attributes.subject
Week 6 (Group Aaron, Vatsala, Jin Min, Jing Rou,CK) (K2)

# data[].attributes.body
Extraction, isolation and characterization of
Pyrrolizidine Alkaloids present in Senecio vulgaris Linn
grown in Iraq

Compounds being isolated :
pyrrolizidine alkaloids :
senecionine
seneciphylline

Sources and References:
Hussein Kamil Hamid and Enas J Kadhim. Extraction, isolation and characterization of Pyrrolizidine Alkaloids present in Senecio vulgaris Linn grown in Iraq. Journal of Pharmacognosy and Phytochemistry. 2016; 5(6): 28-37.

# data[].attributes.headline
week 5 (vannisree,syakilla,fatnin, Ku anis, nadhirah husna)

# data[].attributes.subject
week 5 (vannisree,syakilla,fatnin, Ku anis, nadhirah husna)

# data[].attributes.body
Ligand-based virtual screening and molecular docking of two cytotoxic compounds isolated from Papaver lacerum
compouns name:
1)Tyrosol-1-O-β-xylopyranosyl-(1→6)-O-β-
glucopyranoside
2)5-O-(6-O-α-rhamnopyranosyl-β-
glucopyranosyl) mevalonic acid
Sources and references:
https://www.sciencedirect.com/science/article/pii/S1874390018306128

# data[].attributes.body
(Syafika, Marsha, Izzani, balqis, Izzati) (K2)

Natural products with calmodulin inhibitor properties

compound:
1) Stellettamide A
2) Pyridindolol

Source and References :
https://www.sciencedirect.com/science/article/pii/S0031942207001264

# data[].attributes.body
(HUSNA, KU ANIS, SYAKILLA, VANISREE,FATNIN)

High-throughput Preparation ofAntibacterial Polymers from Natural Product Deerivatives via Hantzsch Reaction.

The Hantzsch reaction consists of four common components:
(1) aldehyde
(2) b-ketoester
(3) 1,3-diketone,
(4) NH4OAc

compound produce by Hantzsch reaction:
1. 1,4-dihydropyridines (1,4-DHPs)

Source and Reference:

https://reader.elsevier.com/reader/sd/pii/S2589004219304997?token=304CD965DBFC76396A2FE36EC6279F82A98E9F3E8C938D941BA4BC7464645B0C81689996AF881DE66F38D3B726C62D5B

# data[].attributes.headline
Week 5(amin, danesh,tarshini, putri,amira)(k2) 

# data[].attributes.subject
Week 5(amin, danesh,tarshini, putri,amira)(k2) 

# data[].attributes.body
Creating and screening natural product libraries
compounds:
1)patulin
2)gracilin A
Source and reference:
https://pubs.rsc.org/en/content/articlelanding/2020/np/c9np00068b#!divAbstract

# data[].attributes.headline
Week 6(amin, danesh,tarshini, putri,amira)(k2) 

# data[].attributes.subject
Week 6(amin, danesh,tarshini, putri,amira)(k2) 

# data[].attributes.body
Antimalarial Natural Product Drug Discovery

compounds:
-phloroglucinol
-sesquiterpene lactone
source:
https://kingstonchem.wp.prod.es.cloud.vt.edu/home/antimalarial-natural-product-drug-discovery/

# data[].attributes.headline
Week 7 (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)

# data[].attributes.subject
Week 7 (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)

# data[].attributes.body
Identification of Coronavirus Isolated from a Patient in Korea with COVID-19

name of virus being isolated from  coronavirus (SARS-CoV-2):

1. BetaCoV/Korea/KCDC03/2020

source and reference:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045880/

# data[].attributes.attachment_link.readable_text
Introduction

Coronavirus is an RNA virus consisting of positive-sense single-stranded RNA of approximately 27-32 kb. Coronavirus belong to the family Coronaviridae, which comprises of alpha, beta, delta, and gamma coronaviruses [ 1, 2]. As the name indicates, the spherical external spike protein displays a characteristic crown shape when observed under an electron microscope [ 3, 4]. The virus is known to infect a wide range of hosts including humans, other mammals, and birds. Infected hosts exhibit different clinical courses, ranging from asymptomatic to severe symptoms in their respiratory, digestive, and genital organs [ 1, 2]. There are 6 known coronaviruses that typically cause infection in humans. Among these, coronavirus 229E, OC43, NL63, and HKU1 generally cause mild cold-like symptoms, whereas severe acute respiratory syndrome-coronavirus (SARS-CoV) in 2003, and Middle East respiratory syndrome-coronavirus (MERS-CoV) in 2012, caused severe respiratory diseases such as pneumonia and death [ 5, 6].

Following the first outbreaks of unexplained pneumonia in Wuhan, China, in late 2019, a new coronavirus was identified as the causative agent in January 2020 [ 7]. As of February 11 th, 2020, a total of 45,000 cases of pneumonia, have been reported from 26 countries, including China. Approximately 96.8% of all cases have been reported in China, and patients in the Hubei province account for 75% of all cases [ 8- 10]. In Korea, the first case was reported on January 20, 2020, when SARS-CoV-2 was detected in a traveler entering Korea from Wuhan, China [ 11].

This study reports the full genome sequencing of SARS-CoV-2 isolated from putative the 2019 novel coronavirus disease (COVID-19) patients in Korea, by cell culture. The isolated SARS-CoV-2 was named BetaCoV/Korea/KCDC03/2020.

Materials and Methods

1. Clinical specimens and RNA extraction

Nasopharyngeal and oropharyngeal swab and sputum samples were collected from symptomatic patients to detect SARS-CoV-2 by real-time reverse transcriptase (RT)-PCR. RNA was extracted from clinical samples with a QIAamp viral RNA mini kit (QIAGEN, Hilden, Germany) following the manufacturer's instructions. All specimens were handled under a biosafety cabinet according to laboratory biosafety guidelines of Korea Centers for Disease Control and Prevention for COVID-19.

2. Real-time RT-PCR

The optimal concentration of primers and probes, which were synthesized using a published sequence [ 12], was determined with the RNA transcripts of SARS-CoV. The primer and probe sequences used for RNA-dependent RNA polymerase gene detection were: 5′-GTGARATGGTCATGTGTGGCGG-3′ (Forward), 5′-CARATGTTAAASACACTATTAGCATA-3′ (Reverse) and 5′-CAGGTGGAACCTCATCAGGAGATGC-3′ (Probe in 5-FAM/3′-BHQ format) and the primer and probe sequences used for E gene detection were: 5′-ACAGGTACGTTAATAGTTAATAGCGT-3′ (Forward), 5′-ATATTGCAGCAGTACGCACACA-3′ (Reverse) and 5′-ACACTAGCCATCCTTACTGCGCTTCG-3′ (Probe in 5-FAM/3′-BHQ format). A 25-μL reaction was setup that contained 5 μL of RNA, 12.5 μL of 2 × reaction buffer provided with the Agpath IDTM 1 step RT-PCR system (Thermo Fisher Scientific, Waltham, USA), 1 μL of 25 × enzyme mixture, 1 μL of forward and reverse primers at 10 pM, and 0.5 μL of each probe at 10 pM. Reverse transcription was performed at 50°C for 30 minutes, followed by inactivation of the reverse transcriptase at 95°C for 10 minutes. PCR amplification was performed with 40 cycles at 95°C for 15 seconds and 60°C for 1 minute using an ABI 7500 Fast instrument (Thermo Fisher Scientific).

3. Virus isolation

The virus was isolated from nasopharyngeal and oropharyngeal samples from putative COVID-19 patients. Oropharyngeal samples were diluted with viral transfer medium containing nasopharyngeal swabs and antibiotics (Nystadin, penicillin-streptomycin 1:1 dilution) at 1:4 ratio and incubated for 1 hour at 4°C, before being inoculated onto Vero cells. Inoculated Vero cells were cultured at 37°C, 5% CO ₂ in 1× Dulbecco's modified Eagle's medium (DMEM) supplemented with 2% fetal bovine serum and penicillin-streptomycin. Virus replication and isolation were confirmed through cytopathic effects, gene detection, and electron microscopy. Viral culture of SARS-CoV-2 was conducted in a biosafety Level-3 facility according to laboratory biosafety guidelines of Korea Centers for Disease Control and Prevention.

4. Next generation sequencing of viral full-length genome

Using reverse transcriptase, cDNA was synthesized from RNA extracted from the cultured cell medium in which the virus was replicated. A next generation sequencing (NGS) library was constructed after amplifying the full-length genes of the isolates using the synthesized cDNA and primers designed based on published SARS-CoV-2 DNA sequence. The prepared library was purified and analyzed with Miseq 150 PE. De novo assembly was performed on the sequenced product using Megahit to secure a full-length genome.

5. Sequencing analysis

Gene sequencing was performed using CLC Main Workbench 7.9.1. Alignment was conducted using human and animal coronavirus sequences registered in Global Initiative on Sharing All Influenza Data (GISAID) and NCBI GenBank. The phylogenetic tree was analyzed using MEGA6 with the neighbor-joining method, maximum composite likelihood-parameter distance matrix, and bootstrap values of 1,000 replicates.

6. Transmission electron microscopy

For transmission electron microscopy, the inoculated cells were prefixed by incubating in 2% paraformaldehyde and 2.5% glutaraldehyde in 0.1 M phosphate buffer (pH 7.4) to prevent the autolysis of the cells infected with virus. To minimize the chemical reaction between pre- and post-fixation, the slides were washed 3 times using the same buffer as in the fixative solution and post-fixed with 1% osmium tetroxide. After washing 3 times with deionized water, en bloc staining was performed using 0.5% uranyl acetate. Thereafter, 30%, 50%, 70%, 80%, 90%, and 100% ethanol were used sequentially in ascending concentration for dehydration, which was substituted with propylene oxide. The slides were then embedded in Epon812 plastic resin, and polymerized at 70°C for 48 hours. The prepared plastic block was cut to 70-nm thick sections using an ultramicrotome and mounted on a 100-mesh nickel grid, and electrostained with 5% uranyl acetate. The sections were observed with a transmission electron microscope (Libra120, Carl Zeiss, Germany) at an acceleration voltage of 120 kV [ 13- 15].

Results

1. Virus isolation from Vero cells

Following inoculation of Vero cells with the nasopharyngeal and oropharyngeal samples, they were observed at 24-hour intervals, and the cytopathic effects were observed from 3 days after inoculation (). The inoculated cells were harvested on the 4 th day when more than 80% of the cells exhibited cytopathic effects. Virus replication was confirmed using real-time RT-PCR with RNA extracted from the cell culture medium. The Ct values were 14.40 and 18.26 for the nasopharyngeal and oropharyngeal samples, respectively, which were lower than the cycle threshold (Ct) values of 20.85 and 21.85 in the pre-inoculated samples. The number of virus copies in the samples before inoculation was 7.6 × 10 ⁸ and 3.9 × 10 ⁸ copy/mL, respectively, and increased by 10-70-fold to 5.4 × 10 ¹⁰ and 4.2 × 10 ⁹, respectively, in the cell culture supernatants.

2. Analysis of the structure of the virus by electron micrographs

The structure of the virus in the cytoplasm of 3-day post-inoculation cells was examined by electron microscopy (). Coronavirus-specific morphology was observed. Virus particle size ranged from 70-90 nm and the virus was observed in a wide range of intracellular organelles, especially in vesicles.

3. Full-length genome and phylogenetic analysis

After inoculating cells with the nasopharyngeal and oropharyngeal samples, RNA was extracted from the virus-replicated cell culture medium. The RNA was amplified with primers for full-length gene analysis, and NGS was performed using Miseq. De novo assembly of the NGS sequence secured 28,818 bp of the full-length gene. The acquired gene was compared with 57 human and animal coronaviruses, including Wuhan/IVDC-HB-01/2019(GISAID accession ID: EPI_ISL_402119~121), which was first reported in Wuhan, 54 reported full-length SARS-CoV-2 genes, Bat-SARS-like CoV, and human SARS-CoV (). The analysis showed that the sequence was included in the same cluster as the previously reported SARS-CoV-2 sequence and showed high homology of > 99.5% with other isolated SARS-CoV-2 sequences. The virus was named BetaCoV/Korea/KCDC03/2020, and its full-length gene sequence was registered in WHO GISAID (GISAID accession ID: EPI_ISL_407193).

Discussion

As of February 12 th, 2020, 28 cases of COVID-19 have been reported in Korea, with the first case observed in a traveler residing in Wuhan, China. The SARS-CoV-2 was isolated from a Korean patient who had self-administered antipyretics for initial symptoms such as chills and fever. The patient had experienced intermittent coughing with sputum 3 days after the administration of antipyretics. The SARS-CoV-2 could replicate in other cells (Vero E6 and Caco-II cells), in addition to Vero cells (data not shown). The first SARS-CoV-2 was successfully isolated by inoculating human airway epithelial cells with bronchoalveolar-lavage fluid samples from a patient with pneumonia [ 16]. Since human airway epithelial cells (because of their resemblance to pseudostratified mucociliary epithelium) require 4-6 weeks to differentiate in vivo, isolation of SARS-CoV-2 using Vero cells or Caco-II cells is more convenient. Further studies are needed to select more sensitive cell lines suitable for virus isolation from low viral load samples.

The sequence of the suspected novel coronavirus (KCDC03) was analyzed using the sequences of 54 SARS-CoV-2 including 6 human coronaviruses, Bat-CoVs, and 51 SARS-CoV-2 that have been registered in GISAID by several countries including China, and a phylogenetic tree was produced. Results show that the isolate from Korea was clustered with the new coronavirus, SARS-CoV-2 and classified as betacoronavirus. High homology (99.94%-99.99%) was confirmed with the viral sequences reported from other countries, such as those from Wuhan/IVDC-HB-01/2019(GISAID accession ID: EPI_ISL_402119). Homology with bat CoV (bat-SL-CoVZC45), SARS-CoV ( AY278741) and MERS-CoV ( JX869059) was 89.1%, 77.5%, and 50%, respectively. However, the lowest homology of 99.5% was observed with BetaCoV/Wuwhan/IVDCHB-04/2020, which could be because of the inaccurate sequence of IVDCHB-04, Hence, it has been excluded from the comparative analysis in other studies.

Prior to identification of SARS-CoV-2 as the causative agent of the unknown pneumonia in Wuhan, China, pan-CoV RT-PCR was being used to detect SARS-CoV-2 in Korea. The Pan-CoV RT-PCR detects all human coronaviruses and animal-derived coronaviruses (personal communication). Since the release of the SARS-CoV-2 sequence, a real-time RT-PCR method has been established in the diagnosis of COVID-19 patients. Currently, the diagnosis of COVID-19 is based on gene detection via real-time RT-PCR. With the isolation of the causative agent, development of serological tests and rapid diagnostic tests in addition to virus detection will be required.

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Identification of Coronavirus Isolated from a Patient in Korea with COVID-19

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Coronavirus is an RNA virus consisting of positive-sense single-stranded RNA of approximately 27-32 kb. Coronavirus belong to the family Coronaviridae, which comprises of alpha, beta, delta, and gamma coronaviruses [ 1, 2]. As the name indicates, the spherical external spike protein displays a characteristic crown shape when observed under an electron microscope [ 3, 4].

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Week 6 ( Atika, Adilah, Rafiqah, Izzati Sharif, Haiff)

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Week 6 ( Atika, Adilah, Rafiqah, Izzati Sharif, Haiff)

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A Historical Overview of Natural Products in Drug Discovery

Compounds names:
1. Pilocarpine
2. Digitoxin

Source and References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901206/

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Week 7 (kuanis, nadhirah, syakilla, vannisree, fatnin)

Name of compound
1. Kaerenoic acid
2. Abietic acid
3. Proline
4. Pipecolic acid

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Natural products have been the single most productive source of leads for the development of drugs. Over a 100 new products are in clinical development, particularly as anti-cancer agents and anti-infectives. Application of molecular biological techniques is increasing the availability of novel compounds that can be conveniently produced in bacteria or yeasts, and combinatorial chemistry approaches are being based on natural product scaffolds to create screening libraries that closely resemble drug-like compounds. Various screening approaches are being developed to improve the ease with which natural products can be used in drug discovery campaigns, and data mining and virtual screening techniques are also being applied to databases of natural products. It is hoped that the more efficient and effective application of natural products will improve the drug discovery process.

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Natural products have been the single most productive source of leads for the development of drugs. Over a 100 new products are in clinical development, particularly as anti-cancer agents and anti-infectives.

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Midsem Break (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)

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Midsem Break (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)

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Isolation and structure elucidation of siliendines A‒D, new β-carboline alkaloids from Silene seoulensis

So basically, this is a plant that grows well in the northen hemisphere. In this research paper, they successfully isolated 2 alkaloids compound from this plant, well, it is actually 4 but they are unable to name the 3rd and 4th one but structural identifications had been made and being established that 3rd and 4th exist.

1.  1- hydroxy-4-carboxyl-3-acetyl-β-carboline
2.   4-carboxyl-3-methoxycarbonyl-β-carbolinone

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Week 9 (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)

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Week 9 (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)

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Two new phenolic compounds from the leaves of Alnus sibirica Fisch. ex Turcz.

Members of the Alnus species have been used in a number of traditional medicines.  Alnus sibirica Fisch. ex Turcz. (AS) is geographically distributed in Korea, Japan, Northeast China and Russia, and the bark of this plant has been used as an antipyretic, expectorant, antiasthmatic and a health tea for alcoholism.
The previous studies showed that Alnus species is a good source of diarylheptanoids, and that plants of this genus exhibit anti-oxidative, anti-inflammatory, anti-atopic, anti-bacterial and anti-adipogenic activities.

2 phenolic compounds were isolated and antioxidant properties were identified through DPPH and NBT assay.

NAME OF PHENOLIC COMPOUNDS ISOLATED:
1.  4-O-glucopyranosyl-5-O-caffeoylshikimic acid
2.  2,3-digalloyl oregonin

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Abstract

Two new phenolic compounds, 4- O-glucopyranosyl-5- O-caffeoylshikimic acid ( 1) and 2,3-digalloyl oregonin ( 2), were isolated along with eight known phenolic compounds ( 3- 10) from an 80% acetone extract of Alnus sibirica leaves. The chemical structures of these compounds were elucidated using 1D/2D nuclear magnetic resonance and high resolution-MS. The anti-oxidative activities of these compounds were determined by assaying their 1,1-diphenyl-2-picrylhydrazyl radical and nitroblue tetrazolium superoxide anion scavenging activity. All of the isolated phenolic compounds ( 1- 10) exhibited potent anti-oxidative activities. In particular, 2 and 4, which are diarylheptanoids, and 10 which is ellagitannin exhibited excellent anti-oxidative activities with almost the same potency as that of the positive controls L-ascorbic acid and allopurinol.

1. Introduction

Members of the Alnus species have been used in a number of traditional medicines such as cathartics, emetics, galactogogues, febrifuges, hemostatics, parasiticides, vermifuges, skin tonics and astringents (Guo et al. 2001). Alnus sibirica Fisch. ex Turcz. (AS) is geographically distributed in Korea, Japan, Northeast China and Russia, and the bark of this plant has been used as an antipyretic, expectorant, antiasthmatic and a health tea for alcoholism (Lee 1966). Previous studies on the chemical constituents of the Alnus species have led to the isolation of various tannins, flavonoids, diarylheptanoids and triterpenoids (Suga et al. 1972; Terazawa et al. 1984; Aoki et al. 1990; Lee et al. 1992, 1999; Jeong et al. 2000; Choi et al. 2012). These studies have shown that the Alnus species is a good source of diarylheptanoids, and that plants of this genus exhibit anti-oxidative, anti-inflammatory, anti-atopic, anti-bacterial and anti-adipogenic activities (Joo et al. 2009; Lee et al. 2010, 2013; Choi et al. 2012). This paper describes the isolation and structure elucidation of two new phenolic compounds along with eight known phenolic compounds. In addition, the anti-oxidative activities of these compounds were determining by assessing their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and nitroblue tetrazolium (NBT) superoxide anion scavenging activity.

2. Results and discussion

The 80% acetone extract of AS leaves was dissolved in water and filtered using Celite. The resulting filtrate was concentrated and applied to column chromatography using Ambelite XAD-2, Sephadex LH-20, MCI-gel, CHP 20P and ODS-B gel with a reversed phase medium pressure liquid chromatography (MPLC) system, which afforded 10 compounds including two new phenolic compounds ( 1 and 2) (Figure 1). The known compounds ( 3- 10) were identified as alnuside A ( 3, Kuroyanagi et al. 2005), alnuside C ( 4, Kuroyanagi et al. 2005), quercetin ( 5, Dutta et al. 2007), quercitrin ( 6, Lee et al. 2003), hyperoside ( 7, Lee et al. 2003), quercetin-3- O-β-d-glucuronide-methylester ( 8, Pacifico et al. 2013), kaempferol-3- O-α-l-(4″E- p-coumaroyl)-rhamnoside ( 9, Yang et al. 10, Liu et al. 2010) and isocorilagin ( 2008), respectively, by comparing their spectroscopic (MS and nuclear magnetic resonance (NMR)) data with literature values.

Compound 1 was isolated as a pale yellow amorphous powder. High-resolution (HR)-negative FAB-MS ( m/z 497.1295 [M − H] − , calcd for C ₂₂H ₂₅O ₁₃, 497.1299) indicated its molecular formula was C ₂₂H ₂₆O ₁₃. In thin-layer chromatography (TLC), 1 was detected using a UV lamp at 254 nm as a dark brown spot by spraying with FeCl ₃ solution and a yellow spot by spraying with H ₂SO ₄ solution and heating.

The ¹H NMR spectrum of 1 revealed three aromatic protons [δ H 7.18 (d, J = 2.4 Hz, H-2′), 7.03 (dd, J = 2.4, 7.8 Hz, H-6′), 6.84 (d, J = 7.8 Hz, H-5′)] in an ABX spin system and two doublets at δ H 7.70 (d, J = 16.2 Hz, H-7′), 6.33 (d, J = 16.2 Hz, H-8′) of a trans-double bond. The ¹³C NMR spectrum of 1 exhibited one carboxyl group (δ C 167.3) and two hydroxyl bearing aromatic carbons (δ C 148.2 and 146.2). These findings suggested the presence of a caffeoyl moiety.

The ¹H NMR spectrum of 1 showed the presence of a proton singlet at δ H 6.72 (1H, m, H-6), two coupled germinal protons at δ H 2.79 (1H, dd, J = 5.4, 18.6 Hz, H-2a) and 2.30 (1H, dd, J = 5.4, 18.6 Hz, H-2b) and three oxymethine groups appearing at δ H 5.83 (1H, brs, H-5), 4.24 (1H, dd, J = 5.1, 12.6 Hz, H-3) and 4.10 (1H, dd, J = 5.1, 12.6 Hz, H-4). ¹³C NMR spectrum of 1 revealed the presence of a shikimic acid moiety [δ C 167.7 (C-7), 133.4 (C-1), 132.5 (C-2), 78.6 (C-4), 68.2 (C-5), 66.3 (C-3), 31.2 (C-6)].

The ¹H and ¹³C NMR spectra of 1 also revealed a glucopyranosyl moiety, one methylene [δ H 3.85 (m, H-6″a), 3.65 (m, H-6″b)], and five additional methine groups [δ H 4.50 (d, J = 7.8 Hz, H-1″), 3.45 (m, H-3″), 3.34 (m, H-4″, H-5″), 3.23 (m, H-2″)] and at δ C 103.6 (C-1″), 76.8 (C-5″), 76.4 (C-3″), 73.6 (C-2″), 70.2 (C-4″), 61.5 (C-6″). In addition, the large coupling constant ( J = 7.8 Hz) of H-1″ at δ H 4.50 in the ¹H NMR spectrum of 1 suggested that the glucopyranoside was in a β-configuration.

The connectivities of caffeoyl and shikimic acid and glucose were elucidated by heteronuclear multiple bond coherence (HMBC) correlation signals. The HMBC spectrum of 1 showed a correlation between the H-1″ of glucose and C-4 of shikimic acid, and also showed the correlation between H-5 of shikimic acid and carbonyl C-9′ of caffeoyl moiety. Based on these results, compound 1 was elucidated as 4- O-β-d-glucopyranosyl-5- O-caffeoylshikimic acid. Compound 1 is the first reported shikimic acid conjugated with glucose and caffeic acid.

Compound 2 was isolated as a dark yellow amorphous powder. HR-negative FAB-MS ( m/ z 781.1978 [M − H] − , calcd for C ₃₈H ₃₇O ₁₈, 781.1980) indicated its molecular formula was C ₃₈H ₃₈O ₁₈. In TLC, 2 was detected as a dark blue spot by spraying with FeCl ₃ solution, and a brown spot by spraying with H ₂SO ₄ solution and heating.

The ¹H and ¹³C NMR spectra of 2 showed two galloyl groups in the aromatic region [δ H 7.04 (2H, s, galloyl-2, 6) and 7.06 (2H, s, galloyl-2′, 6′)] and [(δ C 165.7 (C-7″″), 165.0 (C-7″″′), 145.0 (C-3″″, 3″″′, 5″″, 5″″′), 138.1 (C-4″″), 138.0 (C-4″″′), 120.4 (C-1″″), 120.3 (C-1″″′), 109.2 (C-6″″, 6″″′), 109.1 (C-2″″, 2″″′)] and one diarylheptanoid glycoside moiety compose of five methylenes [δ H 1.70-1.75 (2H in total, m, H-6), 2.33-2.68 (8H, m, H-1, 2, 4, 6, 7] and a methine [δ H 4.15 (1H, m, H-5) and 1.70-1.75 (2H in total, m, H-6)] and carbonyl carbon C-3 (δ C 207.7), a secondary carbonyl carbon C-5 (δ C 75.2), and five carbons [δ C 28.6 (C-1), 44.8 (C-2), 47.6 (C-4), 37.3 (C-6) and 30.5 (C-7)] as heptanes moiety and two sets of caffeoyl groups [δ H 6.67 (1H, d, J = 7.8 Hz, H-5′), 6.69 (1H, d, J = 7.8 Hz, H-5″, 6.59 (1H, d, J = 2.4 Hz, H-2′), 6.67 (1H, d, J = 2.4 Hz, H-2″), 6.39 (1H, dd, J = 2.4, 7.8 Hz, H-6′) and 6.48 (1H, dd, J = 2.4, 7.8 Hz, H-6″; δ C 115.0 (C-2′), 115.1 (C-2″), 115.3 (C-5′, C-5″) and 119.4 (C-6′, C-6″), 144.6 (C-3′), 144.7 (C-3″), 143.0 (C-4″) and 142.9 (C-4′)] and a xylopyranosyl moiety [δ H 5.32 (1H, m, H-3″′), 5.07 (1H dd, J = 7.8, 9.6 Hz, H-2″′), 4.81 (1H, d, J = 7.8 Hz, H-1″′), 4.04 (1H, m, H-5″′a), 3.95 (1H, m, H-4″′), and 3.48 (1H, m, H-5′b), and δ C 101.2 (C-1″′), 75.7 (C-3″′), 71.7 (C-2″′), 68.4 (C-4″′) and 65.7 (C-5″′)] were observed.

These results indicated that 2 consisted of a diarylheptanoid glycoside (oregonin) and two galloyl groups. The locations of the galloyl units were determined as the C-3″′ and C-2″′ of the xylopyranosyl moiety by a downfield shift of C-3″′ and C-2″′ at δ C 75.7 (C-3″′) and 71.7 (C-2″′) together with an upfield shift of C-4″′ to δ C 68.4 (C-4″′) compared with oregonin (Lee et al. 1992).

The connectivity of the diarylheptanoid with xylose and galloyl groups was further confirmed by HMBC correlations. Especially, the HMBC spectrum of 2 showed a correlation between the H-1″′ of xylose and C-5 of the diarylheptanoid moiety. The HMBC spectrum of 2 also revealed correlations between H-2″′ and H-3″′ of xylose and each C-7″″, 7″″′ of the galloly moiety. Based on these results, the structure of compound 2 was elucidated as 2,3-digalloyl oregonin. Interestingly, a diarylheptanoid-conjugated ellagitannin from the leaves of Alnus hirsuta var. microphylla was previously reported (Lee et al. 1992); however, compound 2 is the first report of a diarylheptanoid-conjugated gallotannin.

Most of the isolated phenolic compounds from the leaves of AS exhibited potent scavenging activities of DPPH radical and NBT superoxide anion (Table 1). The new compound ( 2) which is diarylheptanoid with galloyl moiety and isocorilagin ( 10) which is ellagitannin showed more strong anti-oxidative activity than L-ascorbic acid and almost same potency compared with allopurinol (Table 1).

27 July 2015

In particular, the anti-oxidative activity of 2, which contains a diarylheptanoid with two galloyl moieties, is more potent than that of 3 and 4 whose structures are similar to 2 (Table 1). This result indicates the importance of polyhydroxy groups in the structure for the anti-oxidative effect.

3. Experimental

3.1. General experimental procedures

Column chromatographic isolations were performed using Ambelite XAD-2 (20-50 μm, Fluka AG, Buchs, Switzerland), Sephadex LH-20 (10-25 μm, GE Healthcare Bio-Science AB, Uppsala, Sweden), MCI-gel CHP 20P (75-150 μm, Mitsubishi Chemical, Tokyo, Japan), Toyopearl HW-40F (30-60 μm, Tosoh Corp., Tokyo, Japan) and ODS-B gel (40-60 μm, Daiso, Osaka, Japan). ODS-B gel was also used as a stationary phase for the middle pressure liquid chromatography (MPLC) system. TLC was carried out using a pre-coated silica gel 60 F ₂₅₄ plate (Merck, Darmastadt, Germany) with chloroform, methanol, and water (70:30:4, 80:20:2, volume ratio). Spots were detected under UV radiation (254 nm) and spraying with FeCl ₃ and 10% H ₂SO ₄ or anisaldehyde-H ₂SO ₄ followed by heating. The chemical structures were elucidated by several instrumental analyses. 1D NMR such as ¹H (300 or 600 MHz) and ¹³C (75 or 150 MHz) NMR, 2D NMR such as proton-proton correlation spectroscopy ( ¹H- ¹ H COSY), heteronuclear single quantum coherence, and HMBC experiments were recorded with Gemini 2000 and VNS instruments (Varian, Palo Alto, CA, USA) at the centre for research facilities of Chung-Ang University. HR fast atom bombardment mass spectra were recorded with JMS-600W and JMS-700 instruments (JEOL, Tokyo, Japan) at the National Center for Inter-University Research facilities at Seoul National University.

3.2. Plant material

AS leaves were collected from Mt. Guksabong in Dongjak-gu, Seoul, Korea in August 2010 and its identity was confirmed by Prof. M.W. Lee (Pharmacognosy Lab, Laboratory of Pharmacognosy and Natural Product Derived Medicine, College of Pharmacy, Chung-Ang University) and C.I. Lee (Kwang-Leung Korean National Arboretum in Pocheon, Korea). A voucher specimen (MR2010-08) has been deposited at the herbarium of the College of Pharmacy, Chung-Ang University.

3.3. Extraction and isolation

AS leaves (15 kg) were extracted with 80% acetone at room temperature. The resulting extract was concentrated by removing the acetone under vacuum, which afforded 1062 g of material. After acetone evaporation, water liquid was filtered through Celite 545 (Duksan Pure Chemicals Co. Ltd, Korea). The resulting filtrate (764 g) was applied to Ambelite XAD-2 (20-50 μm, 10 kg, 70 × 50 cm) and eluted using a graded H ₂O, 50-100% MeOH solvent system yielding six fractions (AS-1 to AS-6). Repeated column chromatography of fraction AS-4 (225 g) using a Sephadex LH-20 column (25-100 μm, 2000 g, 10 × 120 cm, 0-100% MeOH in H ₂O) yielded seven subfractions (AS-4-1 to AS-4-7). Fraction AS-4-3 (94 g) was applied to a Sephadex LH-20 column (25-100 μm, 2000 g, 10 × 120 cm, 0-100% MeOH in H ₂O), which yielded eight subfractions (AS-4-3-1 to AS-4-3-8). Repeated column chromatography of fraction AS-4-3-2 using an ODS gel column (50 μm, 150 g, 3 × 50 cm, 0-100% MeOH in H ₂O) and Toyopearl HW-40F (40 μm, 120 g, 3 × 40 cm) yielded [4- O-glucopyranosyl-5- O-caffeoylshikimic acid] ( 1, 370 mg). Fraction AS-4-3-4 (9.79 g) was applied to an MCI gel column (50 μm, 400 g, 3 × 50 cm, 0-100% MeOH in H ₂O) and an ODS gel column (50 μm, 250 g, 3 × 50 cm, 10-100% MeOH in H ₂O) to yield alnuside A ( 3, 80 mg). Subfraction AS-4-3-7 (3.78 g) was applied to an ODS gel column (50 μm, 250 g, 3 × 50 cm, 20-100% MeOH in H ₂O), which yielded quercitrin ( 6, 300 mg) and hyperoside ( 7, 22 mg). Subfraction AS-4-4 was applied to an MCI gel column (50 μm, 400 g, 3 × 50 cm, 0-100% MeOH in H ₂O), from which 13 subfractions (AS-4-4-1 to AS-4-4-13) were obtained. Subfraction AS-4-4-3 was sequentially applied to an ODS gel column (50 μm, 250 g, 3 × 50 cm, 0-100% MeOH in H ₂O), of which subfraction AS-4-4-3-11 was applied to a Toyopearl HW-40F column (40 μm, 120 g, 3 × 40 cm, 0-100% MeOH in H ₂O) to yield isocorilagin ( 10, 55 mg). Likewise, the subfraction AS-4-4-5 was applied to an ODS gel column (50 μm, 250 g, 3 × 50 cm, 0-100% MeOH in H ₂O), which yielded quercetin-3- O-β-d-glucuronide-methylester ( 8, 62 mg). In addition, 2,3-digalloyl oregonin ( 2, 66 mg) was obtained from subfraction AS-4-4-8 by column chromatography with an ODS gel column (50 μm, 250 g, 3 × 50 cm, 0-100% MeOH in H ₂O). Repeated column chromatography of fraction AS-5 (40.85 g) using a Sephadex LH-20 column (25-100 μm, 2000 g, 10 × 120 cm, 50-100% MeOH in H ₂O), yielded seven subfractions (AS-5-1 to AS-5-7). The subfraction AS-5-2 (1.37 g) was applied to an MCI gel column (50 μm, 400 g, 3 × 50 cm, 40-100% MeOH in H ₂O) and an ODS gel column (50 μm, 150 g, 3 × 50 cm, 20-100% MeOH in H ₂O), which yielded alnuside C ( 4, 45 mg). Fraction AS-5-5 (0.97 g) was continuously applied to an ODS gel column (50 μm, 150 g, 3 × 50 cm, 50-100% MeOH in H ₂O), which resulted in kaempferol-3- O-α-l-(4″E- p-coumaroyl)-rhamnoside ( 9, 800 mg). Lastly, quercetin ( 5, 125 mg) was obtained by recrystallisation of AS-5-6 (0.49 g).

3.3.1. 4-O-Glucopyranosyl-5-O-caffeoylshikimic acid (1)

Pale yellow amorphous powder. [α] D: − 149.7° ( c = 0.01, MeOH). IR (KBr) cm ⁻¹: 3391, 1697, 1601, 1517. HR-negative FAB-MS m/ z: 497.1295 [M − H] ⁻ (calcd C ₂₂H ₂₅O ₁₃, 497.1299). ¹H NMR (600 MHz, acetone- d ₆ + D ₂O): δ 7.70 (1H, d, J = 16.2 Hz, H-7′), 7.18 (1H, d, J = 2.4 Hz, H-2′), 7.03 (1H, dd, J = 2.4, 7.8 Hz, H-6′), 6.84 (1H d, J = 7.8 Hz, H-5′), 6.72 (1H, m, H-6), 6.33 (1H, d, J = 16.2 Hz, H-8′), 5.83 (1H, brs, H-5), 4.50 (1H, d, J = 7.8 Hz, H-1″), 4.24 (1H, m, H-3), 4.10 (1H, m, H-4), 3.85 (1H, m, H-6″a), 3.65 (1H, m, H-6″b), 3.45 (1H, t, J = 8.7 Hz, H-3″), 3.34 (2H, m, H-4″, H-5″), 3.23 (1H, m, H-2″), 2.79 (1H, m, H-2a), 2.30 (1H, m, H-2b). ¹³C NMR (150 MHz, acetone- d ₆ + D ₂ O): δ 167.3 (C-7), 166.9 (C-9′), 148.2 (C-4′), 146.2 (C-3′), 145.4 (C-7′), 133.0 (C-1), 132.1 (C-2), 126.4 (C-1′), 121.9 (C-6′), 115.5 (C-5′), 114.3 (C-2′), 114.0 (C-8′), 103.6 (C-1″), 78.1 (C-4), 76.8 (C-5″), 76.4 (C-3″), 73.6 (C-2″), 70.2 (C-4″), 67.8 (C-5), 65.9 (C-3), 61.5 (C-6″), 30.7 (C-6).

3.3.2. 2,3-Digalloyl oregonin (2)

Dark yellow amorphous powder. IR (KBr) cm − 1: 3346, 1708, 1611, 1526. HR-negative FAB-MS m/ z: 781.1978 [M − H] − (calcd C ₃₈H ₃₇O ₁₈, 781.1980) ¹H NMR (600 MHz, acetone- d ₆ + D ₂O): δ 7.06 (2H, s, H-2″″′, 6″″′), 7.04 (2H, s, H-2″″, 6″″), 6.69 (1H, d, J = 7.8 Hz, H-5″, 6.67 (1H, d, J = 2.4 Hz, H-2′), 6.67 (1H, d, J = 7.8 Hz, H-5′), 6.59 (1H, d, J = 2.4 Hz, H-2″), 6.48 (1H, dd, J = 2.4, 7.8 Hz, H-6″), 6.39 (1H, dd, J = 2.4, 7.8 Hz, H-6′), 5.32 (1H, m, H-3″′), 5.07 (1H, dd, J = 7.8, 9.6 Hz, H-2″′), 4.81 (1H, d, J = 7.8 Hz, H-1″′), 4.15 (1H, m, H-5), 4.04 (1H, m, H-5″′a), 3.95 (1H, m, H-4″′), 3.48 (1H, m, H-5″′b), 2.33-2.68 (8H in total, m, H-1, 2, 4, 7), 1.70-1.75 (2H in total, m, H-6). ¹³C NMR (150 MHz, acetone- d ₆ + D ₂ O): δ 207.7 (C-3), 165.7 (C-7″″), 165.0 (C-7″″′), 145.0 (C-3″″, 3″″′, 5″″, 5″″′), 144.7 (C-3″), 144.6 (C-3′), 143.0 (C-4″), 142.9 (C-4′), 138.1 (C-4″″), 138.0 (C-4″″′), 133.7 (C-1″), 132.8 (C-1′), 120.4 (C-1″″), 120.3 (C-1″″′), 119.4 (C-6′, 6″), 115.3 (C-5′, 5″), 115.1 (C-2″), 115.0 (C-2′), 109.2(C-6″″, 6″″′), 109.1 (C-2″″, 2″″′), 101.2 (C-1″′), 75.7 (C-3″′), 75.2 (C-5), 71.7 (C-2″′), 68.4 (C-4″′), 65.7 (C-5″′), 47.6(C-4), 44.8 (C-2), 37.3 (C-6), 30.5 (C-7), 28.6 (C-1).

3.4. Measurement of DPPH radical scavenging activity

Each sample was dissolved in absolute EtOH and added to a DPPH solution (0.1 mM, in absolute EtOH). After mixing gently for 30 min, optical densities were measured at 518 nm using a microplate reader (TECAN, Salzburg, Austria). L-ascorbic acid was used as a positive control.

3.5. Measurement of NBT/superoxide anion scavenging activity

Each sample was dissolved in 50 mM phosphate buffer (pH 7.5) containing 0.05 mM EDTA, 0.2 mM hypoxanthine, and 0.1 mM NBT. Next, xanthine oxidase (1.2 U/μL) was added to the mixture. After mixing gently for 30 min, optical densities were measured at 612 nm using a microplate reader (TECAN). Allopurinol was used as a positive control.

3.6. Statistical analysis

All data were expressed as the mean ± SD. Values were analysed by Student-Newman-Keuls test, and values of p < 0.05 were considered to be significantly different.

4. Conclusion

The activity-guided isolation of A. sibirica yielded 10 phenolic compounds ( 1- 10) including two new compounds, 4- O-β-d-glucopyranosyl-5- O-caffeoylshikimic acid ( 1) and 2,3-digalloyl oregonin ( 2) which are the first reported shikimic acid conjugated with glucose and caffeic acid ( 1) and diarylheptanoid conjugated with gallotannin ( 2).

The phenolic compounds ( 1-10) showed potent antioxidative activities against DPPH and NBT radicals. Especially, 2 and 4 which are diarylheptaoid and 10 which is ellagitannin showed excellent anti-oxidative activities. The results suggest that the leaves of A. sibirica and the phenolic compounds isolated from these leaves are promising source of natural products that can be developed as anti-oxidant agents.

Disclosure statement

No potential conflict of interest was reported by the authors.

Compounds

DPPH radical scavenging activity (μM)

Superoxide anion scavenging activity (μM)

Vit-C

20.50 ± 0.71 k

-

Allopurinol

-

7.51 ± 0.53 b

Notes

1. These authors contributed equally to this work and should be considered as co-first authors.

References

Aoki T , Ohta S , Suga T . 1990. Triterpenoids, diarylheptanoids and their glycosides in the flowers of 3611-3614.Alnus speies. Phytochemistry. 29:

Dutta NK , Mazumdar K , Mishra US , Dastidar SG , Park JH . 2007. Isolation and identification of a flavone (quercetin) from 37-39.Butea frondosa bark. Khimiko-Farmatsevtischeskii Zhurnal. 41:

Lee SJ . 1966. Korea folk medicine. Seoul: Seoul National University Publishing Center Press.

Lee MW , Jeong DW , Lee YA , Park MS , Toh SH . 1999. Flavonoids from the leaves of 547-552.Alnus hirsuta. YakhakHoegi. 43:

Lee MN , Song JY , Chin YW , Sung SH . 2013. Anti-adipogenic diarylheptanoids from 2069-2073.Alnus hirsuta var sibirica on 3T3-L1 cells. Bioorg Med Chem Lett. 23:

Lee MW , Tanaka T , Nonaka GI , Nishioka I . 1992. Hirsunin, an ellagitannin with a diarylheptanoid moiety, from 967-970.Alnus hirsuta var microphylla. Phytochemistry. 31:

Suga T , Iwata T , Asakawa Y . 1972. Chemical constituents of the male flower of 2058-2060.Alnus pendula (Betulaceae). Bull Chem Soc Jpn. 45:

Terazawa M , Miyake M , Okuyama H . 1984. Phenolic compounds in living tissue of woods. V. Teddish orange staining in keyamahannoki (601-607.Alnus hirsuta) and hannoki (A. japonica) [Betulaceae] caused by the interaction of hirsutoside and catechol oxidase after cutting the woods. Mokuzai Gakkaishi. 30:

Yang NY , Tao WW , Duan JA . 2010. Antithrombotic flavonoids from the faeces of 1843-1849.Trogopterus xanthipes. Nat Prod Res. 24:

Additional information

Funding

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology [grant number 2010-0022929].

# data[].attributes.attachment_link.title
Two new phenolic compounds from the leaves of Alnus sibirica Fisch. ex Turcz.

# data[].attributes.attachment_link.description
Abstract Two new phenolic compounds, 4- O-glucopyranosyl-5- O-caffeoylshikimic acid ( 1) and 2,3-digalloyl oregonin ( 2), were isolated along with eight known phenolic compounds ( 3- 10) from an 80% acetone extract of Alnus sibirica leaves.

# data[].attributes.body
Rapid isolation and identification of minor natural products by LC–MS, LC–SPE–NMR and ECD: Isoflavanones, biflavanones and bisdihydrocoumarins from Ormocarpum kirkii

Compound name:

Antiplasmodial

Isoflavonoids

Biflavonoids

Neoflavanoids

glucosyl moiety
References:
https://www.sciencedirect.com/science/article/abs/pii/S0031942212001495

# data[].attributes.headline
week 9 (Syakilla, Kuanis, Fatnin, Husna, Vannisree)

# data[].attributes.subject
week 9 (Syakilla, Kuanis, Fatnin, Husna, Vannisree)

# data[].attributes.body
UPLC - MS identification and anticomplement activity of the metabolites of Sophora tonkinensis flavonoids treated with human intestinal bacteria.

Compounds :
1. flavonoid glycoside ( daidzein-4'-glucoside-rhamnoside, sophorabioside, rutin, isoquercitrin, quercitrin, ononin, trifolizhin )
2. flavonoid aglycone ( daidzein, genistein, quercetin, formononetin, maackiain)
3. isoprenylated flavonoid ( kurarinone, sophoradin, sophoradochromene, 2-(3-hydroxy-2,2-dimethyl-8-isopentenyl-6-chromanyl)-7-hydroxy-8-isopentenyl-4-chromanone, sophoranone, sophoranochromene)

# data[].attributes.headline
Week 11 (Group Aaron/Vatsala/Jin Min/Jing Rou/ CK)(K2)

# data[].attributes.subject
Week 11 (Group Aaron/Vatsala/Jin Min/Jing Rou/ CK)(K2)

# data[].attributes.body
Isolation and bioactive evaluation of flavonoid glycosides from Lobelia chinensis Lour using two-dimensional liquid chromatography combined with label-free cell phenotypic assays

Flavonoid glycosides are widespread in herbs and often used as medicines and nutraceuticals because of good bioactivities and low toxicities. However, due to their structural complexity and diversity, it is high challenge to isolate flavonoid glycosides and evaluate their bioactivities.  In this study, to solve this problem, a new method for separation and preparation of novel flavonoid glycosides from Lobelia chinensis Lour

(L. chinensis) was developed. This was the first time to use  a structure-guided method development strategy 2D-HILIC

× RPLC system.

Name of flavonoid that isolated from the Lobelia chinensis Lour are as follow:
1. apigenin 7-O-rutiboside
2. luteolin
3. lobetyolin
4. diosmin
5. linarin

# data[].attributes.headline
Week 8 (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)

# data[].attributes.subject
Week 8 (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)

# data[].attributes.body
Isolation, identification and characterization of endophytic bacteria from medicinal plant Tinospora cordifolia.

Okay, so Endophytic bacteria are bacteria detected inside surface-sterilized plants or extracted from inside plants and having no visibly harmful effects on the plants.

In this research paper, they successfully isolated 38 endophytic bacterial species from the plant species Tinospora Cordifolia.  The Endophytic bacteria can be used to generate bioactive metabolites which can be explored to control diseases and promote health of humans, animals and plants. Besides, they can be surveyed for novel medicines, antibiotics, biofertilizers, biopesticides etc.

Name of the endophytic bacteria isolated from plant species Tinospora Cardifolia are as follows.

1.  Bacillus cereus strain CCM 2010
2.  Bacillus albus strain MCCC1A2146
3.  Bacillus subtilis strain DSM10
4.  Pseudomonas chengduensis strain MBR
5.  Bacillus cereus strain IAM 12605
6.  Bacillus subtilis subsp. spizizenii strain NBRC101239
7.  Bacillus toyonensis strain BCT-7112
8.  Bacillus paranthracis strain MCCC 1A00395
9.  Aneurinibacillus danicus strain DB4
10.  Aneurinibacillus aneuriniliticus strain (muruyama)
11.  Pseudomons mendocina strain ATCC 25411
12.  Bacillus velenzensis strain FZB42
13.  Bacillus subtilis strain DSM 10
14.  Bacillus nematocida strain B-16
15.  Bacillus tropicus strain MCCC1A01406
16.  Bacillus cereus strain JCM2152
17.  Aneurinibacillus aneurinilyticus strain (Muruyama)
18.  Bacillus aryabhattai strain B8W22
19.  Bacillus subtilis strain IAM 12118
20.  Bacillus aryabhattai strain B8W22
21.  Bacillus subtilis strain DSM22
22.  Bacillus aryabhattai strain B8W22
23.  Bacillus aryabhattai strain B8W22
24.  Bacillus safensis strain FO-36b
25.  Bacillus aryabhattai strain B8W22
26.  Bacillus paramycoides strain MCCC 1A00732
27.  Bacillus licheniformis strain NBRC 12200
28.  Bacillus megaterium strain IAM13418
29.  Bacillus aryabhattai strain B8W22
30.  Bacillus amyloliquifaciens strain NBRC 15535
31.  Bacillus aerius strain 24 K
32.  Bacillus subtilis subsp. inaquasorum strain BGSC 3A28
33.  Pseudomonas sihuiensis strain WM2
34.   Bacillus pumilus strain NBRC 12092
35.  Bacillus paramycoides strain MCCC1A04098
36.  Bacillus albus strain MCCC1A02146
37.  Bacillus albus strain MCCC1A02146
38.  Aneurinibacillus danicus strain DB4

# data[].attributes.headline
Week 10                   (Group Aaron/Vatsala/Jin Min/Jing Rou/CK)          

# data[].attributes.subject
Week 10                   (Group Aaron/Vatsala/Jin Min/Jing Rou/CK)          

# data[].attributes.body
Isolation and identification of phenolic compounds from
Gynura divaricata leaves

Gynura genus belongs to the family Asteraceae, consisting
of 12 species in China. Many species are edible medicinal
plants and the leaves are also used as a vegetable by the
locals in Southwestern China.
G. divaricata is a traditional
Chinese medicinal plant, which is called “Bai Bei San Qi”
in Chinese. It has a long history of use for treatment of
diabetes in the folk medicine.
This was the first time to use the HPLC-DAD-ESIMS
method to identify the phytochemicals of the genera Gynura. Moreover, compounds (6) and (7) have been isolated for the first time from the genus Gynura.

Six flavonols and one Dicaffeoylquinic acid were isolated from the leaves of Gynura divaricata  were identified as follows:

(1) quercetin

(2) kaempferol
(3) kaempferol-3-O-β    dglucopyranoside
(4) quercetin-3-O-rutinoside
(5) kaempferol-3,7-di-O-β-d-glucopyranoside
(6) kaempferol-3-O-rutinoside-7-O-β-d-glucopyranoside
(7) 3,5-dicaffeoylquinic acid

# data[].attributes.body
(Group Aaron/Vatsala/Jin Min/Jing Rou/CK)
Isolation and characterization of flavonoid derivatives with anti-prostate

cancer and hepatoprotective activities from the flowers of Hosta plantaginea

(Lam.) Aschers

Resluts: Four new flavonol-lignan heterodimers (1–4), together with nine known flavonoid derivatives (5–13)

were isolated from this plant for the first time. Among them, some compounds exhibited moderate anti-prostate

cancer and hepatoprotective activities.

Conclusion: Compounds 1, 2, 5, and 6 showed anti-prostate cancer activities using the LNCaP prostate cancer

cells with IC50 values of 17.84, 33.26, 54.13, and 81.55 μg/mL, and compounds 3, 4, 8, and 9 exhibited

moderate hepatoprotective activities, respectively.

1) 2-(5′-allyl-4‴,9‴-di-

hydroxyphenyl-furan)-3-hydroxy-7-methoxy-8-(6″,7″-dimethyl-furan-

2″-one)-chromen-4-one

2) 2-(5′-allyl-3‴,5‴,9‴-trihydroxy-4‴-meth-

oxyphenyl-furan)-3-hydroxy-7,8-furan-ring-chromen-4-one

3) 2-(3′-

isopropyl-7''-(4″-hydroxy-3″-methoxyphenyl)-9″-hydroxy))-benzo-[1,4]

dioxin-3,5-dihydroxy-7-methoxy-8-prenyl-chromen-4-one

4) 2-(3′-

acetyl-7''-(4‴-hydroxyphenyl)-9‴-hydroxy))-benzo-[1,4]dioxin-3-hy-

droxy-12,13-dimethyl-chromene-8-prenyl-chromen-4-one

5) 2,3-dehydrosilychristin
6) silychristin A
7) silybin A
8) 3-hydroxyhydnocarpin-D
9) sinaiticin
10) cycioheterophyllin (10)
11) rhynchospermin
12) apollinine
13) lanceolatin-A

# data[].attributes.body
syakilla, fathnin, vannisree, husna

Bioassay-guided isolation and identification of antidiabetic compounds fromGarcinia cowaleaf extract

1) decahydro-1H-xanthene derivative
2) garciniacowone K (1)

Source and Reference
https://reader.elsevier.com/reader/sd/pii/S2405844020304709?token=222FA91C3EA72F22C02BD487754DE270CACA455E3702FE8CE240D8B68F1485BB32EDF767F21B4B99E880536BCEB1DE9B

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Week 10 (syakilla, fatnin, anis, vannisree, nadhirah husna)
Antibacterial activity of compounds isolated from Caesalpinia coriaria (Jacq) Willd against important bacteria in public health
Isolated compound
- methyl gallate
-gallic acid
Source and reference : https://www.sciencedirect.com/science/article/abs/pii/S0882401018320345

# data[].attributes.body
OK, two groups submitted. We want more group to share the isolated components yeah!
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OK, two groups submitted. We want more group to share the isolated components yeah!
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The Alkaloids and Bioactivities of Ethanol Extract from a Traditional Remedy of Vietnam

compound names:
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2) berberine


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Isolation and Identification of the Five Novel Flavonoids from Genipa americana Leaves

Novel compounds being isolated:
1. quercetin-3-O-robinoside
2. kaempferol-3-O-robinoside
3. isorhamnetin-3-O-robinoside
4. kaempferol-3-O-robinoside-7-O-rhamnoside (robinin)
5. isorhamnetin-3-O-robinoside-7-rhamnoside

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Antioxidant and anticholinesterase potential of Ferulago cassia with farther bio-guided isolation of active coumarin constituents

Compounds being isolated
1) peucedanol 
2) suberosin 
3) grandivitinol  
4) umbelliferone 
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Chemical composition, antioxidant and antibacterial activities of Tamarix balansae J. Gay aerial parts 
compund involve : 
1) Afzelin
2) rhamnocitrin 

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Natural products: Potential lead compounds for the treatment of endometriosis

Compound involve:
1. Ginsenoside Rf
2. Curcumin

Source and references:
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Application of a Catalytic Asymmetric Povarov Reaction using Chiral Ureas to the Synthesis of a Tetrahyroquinoline Library
Compounds involve:
1) martinelline
2) oxamniquine

Source and reference:
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Natural Products in Drug Discovery

Compound names :
1) Paclitaxel
2) Pseudohypericin

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Week 3 
Alya, syikin, syiba, fara, rabiatul 
Biocarbon from peanut hulls and their green composites with bionased poly(trimethlene terephthalate) (ptt) 

Material 
Peanuts hulls 
https://www.nature.com/articles/s41598-020-59582-3.pdf
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Week 3 (damiya,huda,aina,farhah, saran) (k2)
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Anonymous
1mo
Week 3 (damiya,huda,aina,farhah, saran) (k2)
A CONTINUING SOURCE OF NOVEL DRUG LEADS

Compounds names:
1) khellin 
2) sodium chromoglycate 
3) galegine 
4) metformin
5) papaverine 
6) verapamil 

Source & Reference:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672862/

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Week 4 (Rafiqah, Haiffa, Atika, Izzati Sharif, Adilah)
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Rafiqah Rozak
20d
Week 4 (Rafiqah, Haiffa, Atika, Izzati Sharif, Adilah)
Konamycins A and B and Rubromycins CA1 and CA2, Aromatic Polyketides from the Tunicate-Derived Streptomyces hyaluromycini MB-PO13T.

Compounds names :
1. Konamycins A and B
2. Rubromycins CA1 and CA2

Source and References :
Harunari, E., Imada, C., & Igarashi, Y. (2019). Konamycins A and B and Rubromycins CA1 and CA2, Aromatic Polyketides from the Tunicate-Derived Streptomyces hyaluromycini MB-PO13T [Review-article]. Journal of Natural Products, 82(6), 1609–1615. 
https://doi.org/10.1021/acs.jnatprod.9b00107

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week 4 ( Syafika , Izzani, Marsha, Balqis , Izzati )(k2)
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1mo
week 4 ( Syafika , Izzani, Marsha, Balqis , Izzati )(k2)
 Access to new highly potent antileukemia, antiviral and antimalarial agents via hybridization of natural products (homo)egonol, thymoquinone and artemisinin 

compound names :
1. dihydroartemisinin
2. artesunic acid 
3. egonol
4. homoegonol
5. artemisinin
6. thymoquinone 
7. chloroambucil 


source & reference:
https://www.sciencedirect.com/science/article/pii/S0968089618307004
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Week 5 (Group Aaron, Vatsala, Jin Min, Jing Rou & CK) (K2)
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1mo
Week 5 (Group Aaron, Vatsala, Jin Min, Jing Rou & CK) (K2)
Isolation of terpenoids from Pimpinella anisum essential oil by high-performance counter-current chromatography

Compounds name : 
1. linalool
2. terpinen-4-ol
3. alpha-terpineol

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Week 3 (syakilla,fatnin, anis,vannisree,nadirah husna) (k2) Natural products: Potential lead compounds for the treatment of endometriosis
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Anonymous
17d
Week 3 (syakilla,fatnin, anis,vannisree,nadirah husna) (k2) Natural products: Potential lead compounds for the treatment of endometriosis
Compounds name:
1. Curcumin
2.Ginsenoside Rf
3.Alpha-lipoic acid mixture
4.Melatonin
5.Scutellarin
6.Crocin
7.Genistein
8.Daidzein-rich isoflavone aglycones
source and reference of the compound
https://www.sciencedirect.com/science/article/pii/S0301211519305342

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week 4 (Aina,najwa,saran,huda dan damia)
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Anonymous
1mo
week 4 (Aina,najwa,saran,huda dan damia)
Post-column in-source derivatisation in LC-MS: a tool for
natural products characterisation and metabolomics

compound involve:
-cyloartanes
-cynamin

https://onlinelibrary.wiley.com/doi/abs/10.1002/pca.2926?af=R
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Week 4 (Amin, Danesh, Tarshini, Amira, Putri)(k2)
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1mo
Week 4 (Amin, Danesh, Tarshini, Amira, Putri)(k2)
The first synthesis of phenylpropanoid derivative bromophenols including natural products: Formation of an indene derivative compound

Compounds names : 
1.  red algae Rhodomela confervoides 
2. Symphyocladia latiuscula

Source & reference :
https://www.sciencedirect.com/science/article/pii/S0040402020301186
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week 4 (syakillla, fatnin, anis, nadirah, husna, vannisree) (k2) A review of the literature and latest advances in research of Piper sarmentosum.
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Anonymous
1mo
week 4 (syakillla, fatnin, anis, nadirah, husna, vannisree) (k2) A review of the literature and latest advances in research of Piper sarmentosum.
compounds name :
1. pellitorne
2. sarmentine
3. 1-piperettyl pyorrolidine
4. guneensine
5. brachyamide B
6. brachystamide

source and references :
https://www.tandfonline.com/doi/ref/10.3109/13880209.2011.654229?scroll=top

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Week 5 (Marsha, Balq
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1mo
Week 5 (Marsha, Balqis, Ika, Izzani, Zatisha) (K2) 

Isolation and structure elucidation of cyclopeptide alkaloids from the leaves of Heisteria parvifolia. 

Compound names:
1) cycloheisterin
2) anorldianine

Source & Reference:
https://www.sciencedirect.com/science/article/pii/S0031942219302468
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Week 5, ( group saran,aina,najwa, huda,damiya)
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Anonymous
1mo
Week 5, ( group saran,aina,najwa, huda,damiya)
Anticancer activity of natural compounds from plant and marine environment


Compounds name
1) camptothecin 
2) podophyllotoxin 
3) geniposide 
4) colchicine  

Source and reference 

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good sharing guys!!
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Anonymous
1mo
good sharing guys!!
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WEEK 5 (N.N.Izzati, Rafiqah, Atiqa, Adilah, Haiffa)
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aty sharieff
1mo
WEEK 5 (N.N.Izzati, Rafiqah, Atiqa, Adilah, Haiffa)
Modified Eremophilanes from Parasenecio hastatus and Their Neuroprotective Activities.

New compound that is modified from eremophilane
1)      Furanoeremophilane-type skeleton
2)      Rare C14 nor-eremophilane-type skeleton
3)      Eremophilane lactone-type skeleton
 
Source and references:
Tingting Liu, Haibo Wu, Jing Zhang, Wenjie Deng, and Luowenlei Yang
Journal of Natural Products 2020 83 (2), 185-193
DOI: 10.1021/acs.jnatprod.9b00217

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OK, two groups submitted.
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Anonymous
1mo
OK, two groups submitted. We want more group to share the isolated components yeah!
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Anonymous
16d
OK, two groups submitted. We want more group to share the isolated components yeah!
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Week 3 (izzani, balqis, marsha, syafika, izzati) (k2)
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Anonymous
15d
Week 3 (izzani, balqis, marsha, syafika, izzati) (k2)
The Alkaloids and Bioactivities of Ethanol Extract from a Traditional Remedy of Vietnam

compound names:
1) palmatine 
2) berberine


Source and reference :

http://www.eurekaselect.com/168727/article
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Week 3 (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)
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Aaron Yang
6d
Week 3 (Group Aaron/Vatsala/Jin Min/Jing Rou/CK) (K2)
Isolation and Identification of the Five Novel Flavonoids from Genipa americana Leaves

Novel compounds being isolated:
1. quercetin-3-O-robinoside
2. kaempferol-3-O-robinoside
3. isorhamnetin-3-O-robinoside
4. kaempferol-3-O-robinoside-7-O-rhamnoside (robinin)
5. isorhamnetin-3-O-robinoside-7-rhamnoside

Source & Reference: https://www.mdpi.com/1420-3049/23/10/2521
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Week 6 (Group Aaron, Vatsala, Jin Min, Jing Rou,CK) (K2)
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Anonymous
26d
Week 6 (Group Aaron, Vatsala, Jin Min, Jing Rou,CK) (K2)
Extraction, isolation and characterization of 
Pyrrolizidine Alkaloids present in Senecio vulgaris Linn 
grown in Iraq

Compounds being isolated :
pyrrolizidine alkaloids :
senecionine 
seneciphylline

Sources and References:
Hussein Kamil Hamid and Enas J Kadhim. Extraction, isolation and characterization of Pyrrolizidine Alkaloids present in Senecio vulgaris Linn grown in Iraq. Journal of Pharmacognosy and Phytochemistry. 2016

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(Group Aaron/Vatsala/Jin Min/Jing Rou/CK)
Efficient extraction and isolation of skimmianine from New Caledonian plant Medicosma leratii and evaluation of its effects on apoptosis, necrosis, and autophagy

Compounds isolated:
1) Skimmianine
2) Normelicopidine
3) Normelicopicine
4) Sarcodifurine C

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Week 8 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Week 8 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Natural product analogs
Compound that isolated:
1)Homosedinone
Anti cancer drugs
1) Streptomyces

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Week 13 (Group Aaron/Vatsala/Jin Min/Jing Rou/ Cheang Khai M) - 1 of 2

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Week 13 (Group Aaron/Vatsala/Jin Min/Jing Rou/ Cheang Khai M) - 1 of 2

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In this journal, the researchers isolated flavonoids from our national flower, hibiscus.

The scientific name for our national flower, hibiscus is Hibiscus rosa sinensis.
They used column chromatography method to isolate the flavonoid.

From the petals of the hibiscus, they are able to isolate  Hibiscetin-3-
glucoside (C₂₁H₂₀O₁₄).

Week 14 will be the Grand Finale for this task that starts from Week 3 up until now.

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Week 13 (Group Aaron/Vatsala/Jin Min/Jing Rou/ Cheang Khai M) - 2 of 2

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Week 13 (Group Aaron/Vatsala/Jin Min/Jing Rou/ Cheang Khai M) - 2 of 2

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Since the previous hibiscus journal for week 13, they only isolated one compound, and we are required to find at least two compounds per week, therefore, this is another journal to sum up the amount.

In this journal, they isolated 2 compounds from stem bark of Alstonia boonei, which is a very tall tree widely found in west Africa.

The method that the researchers used to isolate the compound is through column chromatography.

The isolated compound are:

1. tetrahydro-4-(7-hydroxy-10-methoxy-6, 14-dimethyl-15-m-tolylpentadec-13-enyl) pyran-2-one

2. isobutyryl acetate

Some of my thoughts after finishing this task from week 3 to week 14:
In this diversified planet, there are too many compounds in the nature yet to be discovered and studied for their beneficial characteristics. Therefore, I really found that a quote from Aristotle can best suites the journey of our group throughout week 3 to week 14 in discovering new compound each week. The quote is "The more I know, the more I don't know".

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Week 7 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Week 7 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Natural Products: Source of Potential Drugs
Compounds involved:
1) cocaine
2) codeine
3) digitoxin,
4) quinine
5) pilocarpine

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Week 9 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Week 9 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Secondary metabolites
1) Morphine
2) Prostaglandin E1
3) Erythromycin A
4) Benzylpenicillin

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Week 10 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Week 10 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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The function of terpene natural products in the natural world
1) (S)-Linalool
2) Chrysomelidial
3) Cinerin

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Week 12 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Week 12 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Natural products in crop protection
The phytotoxic oligopeptides in the hydrolisate of corn gluten meal used for weed management in organic agriculture:
1)L-alanyl0alanine
The natural herbicides or main component of mixtures used for weed management in organic agriculture :
1)thymol
2)citral

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WEEK 12 ( Syakilla, Fatnin, vannisree, Kuanis, Husna)

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WEEK 12 ( Syakilla, Fatnin, vannisree, Kuanis, Husna)

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Title; Chemical composition and bioactive compounds of garlic (Allium sativum L.) as affected by pre- and post-harvest conditions

Compound of Garlic:

1. Alliin

2. Ajoenes

3. Allyl sulfides

4. 1,2-Vinyldithiin

Source & References:
Retrieved from:
https://www.sciencedirect.com/science/article/pii/S0308814616307099

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Week 14 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Week 14 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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New antibiotics from bacterial natural products
Compounds that isolated:
1) Daptomycin
2) Dalbavancin
3) Oritavancin
4) Efiprestin

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Week 11 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Week 11 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Natural products and plant disease resistance
Terpenoids:
1, sesquiterpene (rishitin, Nicotiana tabacum, I);
2, diterpene (momilactone A, Oryza sativa, I); 3, saponin (medicagenic acid 3-O-glucoside, Dolichos kilimandscharicus, C);
4, saponin (avenacin A, Avena sativa, C). Aliphatic acid derivatives:
5, butyrolactone precursor (tuliposide A, Tulipa spp., C);
6, furanoacetylene (wyerone, Vicia faba, I). Phenolics and phenylpropanoids:
7, hydroxycinnamic acid ester (chlorogenic acid, Nicotiana tabacum, C);
8, flavanone (sakuranetin, Ribes nigrum, C; Oryza sativa, I);
9, aurone (Cephalocereus senilis, I);
10, isoflavone (luteone, Lupinus albus, C);
11, pterocarpan (maackiain, Cicer arietinum, I);
12, pterocarpan (medicarpin, Medicago sativa, I);
13, stilbene (resveratrol, Vitis viniferis, I);
14, chromene (Piper aduncum, C);
15, bibenzyl (batatasin IV, Dioscorea batatas, C),
16, biphenyl (aucuparin, Malus pumila, I);
17, benzofuran (Cotoneasterspp., I);
18, xanthone (Polygala nyikensis, C). Nitrogen- and/or sulphur-containing compounds:
19, benzophenanthridine alkaloid (sanguinarine, Papaver bracteatum, I); 20, benzylisoquinoline alkaloid (berberine, Berberisspp., I);
21, indole (camalexin, Arabidopsis thaliana, I);
22, indole (brassilexin, Brassica spp., I); 23, anthranilamide (Dianthus caryophyllus, I);
24, benzoxazinone (DIMBOA, Zea mays, C);
25, elemental sulphur (Theobroma cacao, I)

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Week 13 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Week 13 (Amin, Danesh, Tarshini, Amira, Putri)(k2)

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Natural products in anticancer therapy
Compound involved:
1) Digoxin
2) Aurantosides
3) Spongistatin 1

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Kuanis, nadhirah husna, syakilla, fatnin, vannisree

Three new triterpenes isolated from the leaves of Neurium oleander :
1. ursane-type triterpene 1
2. oleanane-type triterpene 2,
3. dammarane-type triterpene 15

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Week 14
Nadhirah, Kuanis, Syakilla, Vannisree , Fatnin

Recent Advances In Natural Antifungal Flavonoids And Their Derivatives

Isolated Compound :
Natural Flavonoid
1) Chalcones - 2,4-dihydroxychalcone
2) Flavanones - prenylated flavanone
3) Isoflavanonse - Sedonan A
4) Flavone - prenylated flavone licoflavone
5) Isoflavone - isoflavone derrone
6) Flavonols - myricetin, quercetin, Kaempferol
7) Flavans - catechin , epigallocatechin gallate
8) Isoflavans - Glabridin

Reference :
https://www.sciencedirect.com/science/article/pii/S0960894X19305049