Synthesis And Antibacterial Activity Of New Macrolides Derivatives

Macrolide antibiotics play an important role in the field of antiinfective therapy. The prevalence of antibiotic resistance in bacterial pathogens has been becoming a serious worldwide health problem, several classes of novel chemical modification compounds such as ketolides, acylides and 4”-carbamate macrolides derivatives have good antibacterial activity against macrolide-resistant bacteria.This research work deals with the chemical modification of azithromycin and erythromycin A, based on the literature survey and previous work in our laboratory. About 30 new chemical modified azithromycin analogues are designed and synthesized with 4”-substituted acyl hydrazonyl formate moiety, substituted sulfonyl hydrazonyl formate moiety, and 11,12-carbonate. Totally 66 new chemical modified erythromycin A analogues are designed and synthesized with 9-substituted azine moiety, 6-O-methyl moiety, and 3-decladinosyl-3-O-substituted acyl moiety. All of the above compounds are identified by 1HNMR, 13CNMR, MS and IR.The antibacterial activity of compounds is evaluated in vitro and results indicate that the new compounds showed good antibacterial activity against tested Gram-positive microorganisms, but weak activity against the tested Gram-negative microorganisms. Some azithromycin derivatives showed better antibacterial activity than azithromycin against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus and Gamma streptococcus. Some erythromycin A derivatives showed better antibacterial activity than azithromycin against tested Gram-positive microorganisms. Structure-activity analysis reveals that introduction substituted acyl or sulfonyl hydrazonyl formate into azithromycin improved antibacterial activity against tested Gram-positive microorganisms; erythromycin A derivatives remained 3-cladinosyl have better in vitro activity than that of 3-decladinosyl-3-O-substituted acyl, and 3-decladinosyl-3-hydroxyl analogues demonstrated weaker activity against tested microorganisms.