3.5 Lincosamides
Lincosamides essentially comprise of two clinically useful antibiotics, namely: Lincomycin and Clindamycin; however, their overall general usage has been restricted and limited on account of their inherent potentially fatal side effect called pseudomembranous colitis.**
These two aforesaid antibiotics shall now be treated individually in the sections that follows:
3.5.1 Lincomycin
Synonyms Lincolnensin; Lincolcina; U-10149; NSC-70731;
Biological Source It is produced by Streptomyces lincolensis var. lincolensis.
Chemical Structure Lincomycin has an amide function in its molecule which may have been contributed essentially by an unique strategic combination of amino acid and carbohydrate metabolites.
It is also obtained through stereoselective synthesis by the method of Knapp and Kukkola.***
(2S-trans)-Methyl 6, 8-dideoxy-6-[[(1-methyl-4-propyl-2-pyrrodinyl) carbonyl] amino]-1-thio-perythro-α-D-galacto-octopyranoside; (C18H34N2O6S).
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* H. Aoki et al., J. Antibiot., 29, 492 (1976)
** Pseudomembranous Colitis: Colitis associated with antibiotic therapy. It is indicated by formation of a
pseudomembrane on the mucosa of the colon. The symptoms are: diarrhaea, abdominal cramps, fever and leukocytosis
normally after 4 to 10 days after the start of antibiotic therapy.
*** S. Knapp and P.J. Kukkola, J. Org. Chem. 55, 1637 (1990).
Characteristic Features
1. It is obtained as a free-base invariably.
2. Its dissociation constant is pKa′ 7.6.
3. It is found to be more stable in salt form.
4. It is soluble in methanol, lower alcohols, acetone, ethyl acetate, chloroform; and slightly soluble in water.
Lincomycin Hydrochloride Hemihydrate (C18H34N2, O6S.HCl.½H2O): [Synonyms Frademicina; Lincocin; Mycivin; Wayenecomycin;]
1. It was obtained formerly as needle-like crystals of low specific gravity from aqueous solution by rapid addition of acetone at low temperatures; but nowadays it is mostly obtained as crystals of relatively higher specific gravity, having distinct cubic crystal structure with greater solubility in HCl, by the slow addition of acetone. It has mp 145-147°C.
2. It has specific optical rotation [α]D25 + 137° (water).
3. It is found to be freely soluble in water, methanol, ethanol; and sparingly soluble in most organic solvents other than the hydrocarbons.
Uses
1. It is active against most Gram-positive bacteria, including pneumococci, staphylococci, and streptococci, with the exception of Enterococcus faecalis.
2. Its anaerobic spectra (both Gram-positive and Gram-negative) are also recognized as significant and distinctive.
3. Its use is restricted due to its serious side-effects which essentially include: diarrhoea, occasionally serious pseudomembranous colitis (caused by overgrowth of resistant strains of Clostridium difficile), which may cause serious fatalities especially in aged patients.
Note: Lincomycin inhibits protein biosynthesis due to the blockade of peptidyltransferase site on the 50S subunit of the bacterial ribosomes 70S.
3.5.2 Clindamycin
Synonyms Antirobe; Cleocin; Dalacin C; Klimicin; Sobelin; Clinimycin (rescinded); 7-Deoxy-7(S)-chloro-lincomycin.
Biological Source Clindamycin (7-chloro-7-deoxy-lincomycin) is synthetically derived from lincomycin, which is obtained from the cultures of Streptomyces lincolensis var lincolensis.
Chemical Structure The semi-synthetic derivative is obtained by the chlorination of the lincomycin with resultant inversion of stereochemistry.
(2S-trans)-Methyl 7-chloro-6,7,8-trideoxy-6-[[(1-methyl-4-propyl-2-pyrrolidinyl) carbonyl] amino]-1-thio-L-threo-a-galacto-octo-pyranoside; (C18H33ClN2O5S).
Characteristic Features
1. It is obtained as yellow amorphous solid.
2. It has specific optical rotation [α]D+ 214° (chloroform).
Clindamycin Hydrochloride Monohydrate [C18H33ClN2O5S.HCl.H2O]: [Synonym Dalacin]:
1. It is obtained as white crystals obtained from a mixture of ethanol-ethyl acetate having mp 141-143°C.
2. It has specific optical rotation [α]D+ 144° (H2O).
3. Its dissociation constant is pKa 7.6.
4. It is found to be soluble in water, ethanol, DMF, and pyridine.
Uses
1. It appears slightly more effective quantitatively than its structural analogue lincomycin.
2. It is more readily eliminated from the body. The normal 300 mg dose of lincomycin gives a peak serum level of 2.6 to 3.6 mcg. ml–1 in 1-2 hours, and the normal half-life ranges between 2-4 hours.
3. Clindamycin is reported to be one of the most effective antibiotics against strains of
Bacteroides fragilis, the Gram-negative anaerobe that is responsible for a number of abdominal infections.
4. The antianaerobic property of clindamycin renders it useful in pneumonias caused by anaerobes.
5. Clindamycin phosphate is employed topically for the treatment, control and management of serious acne and vaginally for bacterial vaginosis.
