Synthesis and antibacterial activity against Clostridium difficile of novel demethylvancomycin derivatives

被引：11
作者：
Zhang, Si-Ji [1 ]
Yang, Qing [1 ]
Xu, Liang [2 ]
Chang, Jun [1 ]
Sun, Xun [1 ,3 ]
机构：
[1] Fudan Univ, Sch Pharm, Dept Nat Prod Chem, Shanghai 201203, Peoples R China
[2] Sichuan Univ, W China Sch Pharm, Dept Chem Med Nat Prod, Chengdu 610041, Peoples R China
[3] Fudan Univ, Minist Educ & PLA, Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 15期
基金：
中国国家自然科学基金;
关键词：
Synthesis; Clostridium difficile; Antibacterial activity; Demethylvancomycin; Analogue; SEMISYNTHETIC GLYCOPEPTIDE; TELAVANCIN TD-6424; VANCOMYCIN; INFECTION; ANTIBIOTICS; DISEASE; METRONIDAZOLE; EPIDEMIOLOGY; DIARRHEA;
D O I：
10.1016/j.bmcl.2012.06.039
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
To explore the structure-activity relationships (SAR) of demethylvancomycin (2) and find more effective new chemical entities than known glycopeptides for the treatment of Clostridium difficile (C. difficile), 17 novel N-substituted (N-arylmethylene or -aliphatic substituents) demethylvancomycin derivatives were prepared. These analogues have been evaluated in vitro for their antibacterial activities against C. difficile and Enterococcus faecium (E. faecium). Compounds 5d, 5h, and 5i with N-arylmethylene substituents, structurally similar to Oritavancin, showed more potent antibacterial activity against C. difficile than vancomycin (1) or demethylvancomycin (2). Meanwhile, compound 5k with an undecyl side chain showed the most potent antibacterial activity against E. faecium (vancomycin-resistant strain). Crown Copyright (c) 2012 Published by Elsevier Ltd. All rights reserved.
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收藏
页码：4942 / 4945
页数：4
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