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The first member of this family was chlortetracycline(aureomycin), derived from the soil microorganism Streptomyces Aureofaciens and introduced by Benjamin M. Dugger in 1948.

This was followed by Oxytetracycline produced from Streptomyces rimosus.

Molecular modification by removing the chlorine atom from chlortetracycline produced tetracycline (Achromycin) which was introduced in 1952.these three agents were discovered as a result of extensive screening of antibiotic produced by soil organisms and formed the first group of broad spectrum bacteriostatic antibiotics which are today known as older tetracycline.

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These are class of antibiotic having four cyclic rings. all tetracycline are slightly bitter solid which are weakly water soluble but their hydro-chloride are more soluble. Aqueous solution are unstable. the subsequently developed tetracycline have high lipid solubility, greater potency and some differences

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The Classification is based on the
1.) duration of action
2.) generation

Ø  CLASSIFICATION BASED ONDURATION OF ACTION

1.     Short Acting (half-life 6-8 hours)

Tetracycline

Chlortetracycline

Oxytetracycline

2.     Intermediate acting (half-life 12 hours)

Demeclocycline

Methacycline

3.     Long acting (half-life 16 hours)

Doxycycline

Minocycline

Tygecycline

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Tetracycline enters bacterial cell by either passive diffusion through pores or by active transport system.

Tetracycline are bacteriostatic in nature. They inhibit protein synthesis by binding to 30s ribosome in susceptible organism. this causes interference in formation of aminoacyl-t-RNA to mRNA-ribosome complex.

To understand this, we need to know the normal mechanism of protein synthesis. it is as explained as below: -

Units involved are m-RNA (messenger codons- triplets of 3 nucleotides); 30s subunit of ribosome;50s subunit of ribosome; aminoacyl-t-RNA; A-site, P-site, E –site binding site for t-RNA in 50s subunit.

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STEP 1

Here as shown in the figure initially a t-RNA with growing peptide (M, L, T, are amino acids) chain is in the P-site bounded by codon-anticodon recognition. There is incoming t-RNA with amino acid V.

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STEP 2
The incoming t-RNA binds to the A site by complementary base-pairing.

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STEP 3
ranspeptidation occurs, that is peptide chain on t-RNA on P-site is transferred to t-RNA on A-site. the peptide chain on t-RNA on A-site consist of M, L, T, V amino acids.

t-RNA on P-site has been discharged, i.e. has lost its peptide chain.

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STEP 4
The discharged t-RNA is now transferred from the P-site to the E-site. The t-RNA with the growing peptide chain is translocated from the A-site to the P-site and the ribosome moves on one codon, relative to the messenger.

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STEP 5
The t-RNA from which the peptide chain has been removed is ejected. A new t-RNA, with amino acid ‘M’ attached and with the relevant anticodon moves in to A-site and the whole process is repeated.

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Inhibition

Now after knowing the whole mechanism of protein synthesis the tetracycline works on 30s subunit of ribosome prevents the binding of the aminoacyl t-RNA to m-RNA ribosome complex and does not allows the further synthesis of protein which is explained above. As a result, they prevent the further protein synthesis but do not kill the microorganism so they are bacteriostatic in nature.

The sensitive organism has an energy dependent active transport process which concentrate tetracycline in microorganism intracellularly in gram negative bacteria tetracycline diffuse through porin channels as well. the more lipid soluble drugs (doxycycline, minocycline) entre by passive diffusion.

They also inhibit replication of DNA on the cell membrane at high doses. Tetracycline also bind magnesium, manganese and calcium and this chelating action is probably related to their anti-bacterial activity. It has been suggested that they remove this divalent metallic cation from sites where they are required for enzyme activation.

WHY TETRACYCLINE ARE NOT AFFECTING THE HOST CELL BUT ONLY TO MICROORGANISMS?

Following are two factors are responsible for selective toxicity of tetracycline for the microbes.

1.       The carrier involved in active transport of tetracycline is absent in the host cells.

2.       tetracycline act on 30s ribosome subunit while host have 40s ribosome subunit.

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1.       URL
http://www.uptodate.com/contents/tetracyclines      penetration of tertracycline
https://youtu.be/XEATUcAzE-A                classification of tetracycline

2.       Books

F S K Barar Text Book Of Pharmacology

K.D.Tripathi  Essentials of medical Pharmacology

3.       Video youtube