title: Synthesis and antibacterial activity against Clostridium difficile of novel demethylvancomycin derivatives.
abstract: 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).
authors: Department of Natural Products Chemistry, School of Pharmacy, Fudan University, Shanghai, China.
authors: Si-Ji
authors: SJ
authors: Zhang
authors: Qing
authors: Q
authors: Yang
authors: Liang
authors: L
authors: Xu
authors: Jun
authors: J
authors: Chang
authors: Xun
authors: X
authors: Sun
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016360:Clostridioides difficile / Q000187:drug effects*; D016984:Enterococcus faecium / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin