Synthesis and antibacterial activity of some ester, amides, and hydrazides of 3-carboxyrifamycin S. Relationship between structure and activity of ansamycins.
Esters, amides, and hydrazides of 3-carboxyrifamycin S were synthesized by oxidizing the cyanohydrin of 3-formylrifamycin SV to 3-(cyanocarbonyl)rifamycin S, followed by treatment with alcohols, amines and hydrazines. The in vitro microbiological activity of the derivatives was quite low, especially toward Gram-negative bacteria. This poor activity was not shown to be due to the inadequate inhibiting action on the bacterial DNA-dependent RNA polymerase but to the poor penetration of the compounds through the bacterial cell wall. The microbiological activity was correlated to the chemical properties of the substituent on C3.
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D055598:Chemical Phenomena; D002621:Chemistry; D047029:Lactams, Macrocyclic; D008826:Microbial Sensitivity Tests; D012294:Rifamycins / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D047029:Lactams, Macrocyclic; D012294:Rifamycins