2. TETRACYCLINS
Definition –
• Tetracyclins are octahydro napthacene derivatives which are bacteriostatic
and broad spectrum antibiotics that kill certain infection causing
microorganisms and are used to treat wide variety of infection.
• Tetracyclins antibiotics are members of the tetracycline family.
Nine such compounds -
Tetracycline, Rolitetracycline
Oxytetracycline, Chlortetracycline
Demeclocycline, Meclocycline
Methacycline, Doxycycline
have been introduced into medical use.
• The tetracyclines are obtained by fermentation procedures from Streptomyces
spp. or by chemical transformations of the natural products.
3. STRUCTURE OF TETRACYCLIN
• The tetracycline's are amphoteric compounds, forming salts with either acids
or bases. In neutral solutions, these substances exist mainly as zwitterions. The
acid salts, which are formed through protonation of the enol group on C-2,
exist as crystalline compounds that are very soluble in water.
• These amphoteric antibiotics will crystallize out of aqueous solutions of their
salts, however, unless stabilized by an excess of acid. The hydrochloride salts
are used most commonly for oral administration and usually are encapsulated
because they are bitter.
5. STRUCTURE ACTIVITY RELATIONSHIP
1) All the derivatives containing less than 4 rings are inactive or nearly
inactive.
2) The simplest tetracycline derivative that retains characteristic broad
spectrum activity is 6-demethyl-6-deoxytetracycline.
3) The substituents at carbon 1,2,3,4,10,11,11a and 12 represents hydrophilic
“southern and eastern” faces of molecule can not be voilated drastically to
retain antibacterial activity of class. Retention of the configuration of the
asymmetric centres C-4, C-4a and C-12a is essential, whereas the
configurations at C-5, C-5a and C-6 may be altered cis fusion of ring A and B
with beta OH group at C12 is essential.
“A” ring substituent's can be modified slightly.
4) The enolized carbonyl system from C1 to C3 must remain intact for good
activity.
