Synthesis And Antibacterial Activity Of New 15 Membered Macrolides Analogues

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 and 4"-carbamate macrolides derivatives have good antibacterial activity against macrolide-resistant bacteria.This research work deals with the chemical modification of azithromycin, based on the literature survey and previous work in our laboratory. 14 new chemical modified azithromycin analogues are designed and synthesized with 4" substituted aryl hydrazonyl formoxyl moiety, substituted formoxylhydrazinyl formoxyl moiety, and 11,12-carbonate. 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 better antibacterial activity than azithromycin against tested Gram-positive microorganisms, such as S. aureus (except TM6, TM8, TM1c), S. epidermidis (except TM1, TM2c), and gamma Streptococcus (except TM8), but lower activity against the tested Gram-negative microorganisms. Structure-activity analysis reveals that the indolyl hydrazonyl analogues have better in vitro activity than that of phenyl hydrazonyl analogues against tested Gram-positive microorganisms; the position of the substituent group to aryl can affect the compound's in vitro activity agaist Gram-positive and Gram-negative microorganisms; the methoxyl group to aryl helps to increase the in vitro activity against Gram-positive microorganisms.