Structure activity relationships in lincosamide and streptogramin antibiotics.
Lincomycin is a 6-amino, 6-deoxy-octopyraninose with strong antibiotic activity. To maintain or enhance this activity, one must have the configuration of the first five asymmetric carbons of the sugar residue with the thioglycolic moiety in the alpha-position. The nitrogen on carbon 6 with the R configuration is also a prerequisite for the activity. Substitutions at the level of C-7 as well as the pyrolidine moiety can dramatically enhance this activity. The streptogramin group is composed of a wide variety of structures which can be classified into two subgroups. Group A or M is composed of polyunsaturated cyclic peptolides, e.g. pristinamycin IIA; group B or S is composed of cyclic hexadepsipeptides. Separately, these molecules have a bacteriostatic activity on Gram-positive organisms, whereas in association they exhibit a strong and synergistic bactericidal effect. The 13-OH function of PIIA is essential for antibiotic activity to occur whereas the 15-carbonyl function can be reduced with the retention of the biological properties of the drug. The carbonyl function of PIA can be reduced and the pipecolic moiety can be replaced by other groups without a dramatic influence on the antibiotic activity. The macrocyclic lactone ring is necessary for antibiotic activity.
D000107:Acetylation; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D055231:Lincosamides; D018942:Macrolides; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship; D014769:Virginiamycin / Q000138:chemical synthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D055231:Lincosamides; D018942:Macrolides; D014769:Virginiamycin