标题：Synthesis and antibacterial activity of 4 ''-O-(trans-beta-arylacrylamido) carbamoyl azithromycin analogs
作者：Yan, Mi; Ma, Xiaodong; Dong, Ruiqian; Li, Xin; Zhao, Can; Guo, Zhenzhen; Shen, Yan; Liu, Fang; Ma, Ruixin; Ma, Shutao
作者机构：[Yan, Mi; Ma, Xiaodong; Li, Xin; Zhao, Can; Guo, Zhenzhen; Shen, Yan; Liu, Fang; Ma, Shutao] Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab 更多
通讯作者地址：[Ma, ST]Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, 44 West Culture Rd, Jinan 250012, Peoples R China.
来源：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
关键词：Antibacterial activity; Bacterial resistance; Evaluation; Synthesis; 4; ''-O-(trans-beta-arylacrylamido)carbamoyl azithromycin analogs
摘要：Novel 4 ''-O-(trans-beta-arylacrylamido)carbamoyl azithromycin analogs were designed, synthesized and evaluated for their antibacterial activity against nine significant pathogens using broth microdilution method. A majority of these derivatives maintained the activity of azithromycin against susceptible Streptococcus pyogenes and all the compounds demonstrated remarkably improved activity compared with the references against all the three phenotypes of resistant Streptococcus pneumoniae. In particular, compound 24 exhibited the most potent activity against susceptible Staphylococcus aureus (MIC = 0.5 mu g/mL), S. pneumoniae (MIC = 0.06 mu g/mL) and S. pyogenes (MIC = 0.25 mu g/mL). The most active compound 7 (MIC = 0.015 mu g/mL) against resistant S. pneumoniae expressing the mefA gene, exhibited 512 and 256-fold more potent activity than erythromycin and azithromycin, respectively. Compounds 28 (MIC = 0.5 mu g/mL), 29 (MIC = 0.25 mu g/mL) and 30 (MIC = 0.5 mu g/mL) demonstrated potent activity against resistant S. pneumoniae expressing the ermB gene, which were 256, 512 and 256-fold better than the references, respectively. (C) 2015 Elsevier Masson SAS. All rights reserved.