Synthesis And Antibacterial Activity Of New 4"-derivatives Of Azithromycin

Macrolide antibiotics play an important role in the field of anti-infective therapy. But the emergence of bacterial resistance to many clinical used antibacterial agents has been becoming a serious worldwide health problem. There are several series of compounds such as ketolides and 4"-carbamate macrolide derivatives, which have good antibacterial activity against macrolide-resistant microorganisms.Based on latest research development of macrolides in recent years, I chose 15-membered macrolides as the target for chemical modification. Choosing azithromycin 11,12- boric acid ester as the initial raw materials,We have designed and synthesized a series of 4"-substitued hydrazonyl carbonyl oxy derivatives of azithromycin. The structures of those compounds were confirmed by 1HNMR, 13CNMR, MS and IR.Activity was evaluated in vitro. It was found that the compounds are potent antibacterial agents against gram-positive organisms, all having MIC values below 0.39ug/ml for the Staphylococcus epidermidis, many having MIC values below 0.78μg/ml for the Gamma Streptococcus and the Enterococcus, and as well as improved activity compared to Azithromycin. Except for Shigella flexneri, these compounds demonstrated weak activity against gram-negtive organisms, relatively weaker than Azithromycin. Structure-activity studies revealed that introduction substituted hydrazine into Azithromycin improved antibacterial activity against gram-positive organisms, and reduced antibacterial activity against gram-negtive organisms(except for Shigella flexneri). the antibacterial table of these comounds became narrow relatively.We have synthesized a series of new compounds having potent antibacterial activity against gram-positive organisms and weak activity against most of gram-negtive organisms. Studies on the structure-activity relationship will convenience further studies of new compounds having strong antibacterial activity against susceptible and resistant organisms.