The Synthesis and Antibacterial Activity of Novel 3-O-arylalkylbenzamide Derivatives as FtsZ Inhibitors

A series of novel 3-O-arylalkylbenzamide derivatives as FtsZ inhibitors was designed, synthesized and evaluated for their cell division inhibitory activity against B. subtilis and S. aureus, and in vitro antibacterial activity against various phenotypes of Gram-positive bacteria. This series showed significantly improved on-target activity and in vitro antibacterial activity compared with 3-MBA. Among them, 3-O-alkylbenzamids 4–8 and 3-O-bromoalkylbenzamides 9 and 10 showed significantly improved activity against three phenotypes of S. aureus ATCC25923, S. aureusATCC29213 (MRSA) and S. aureus PR. Preliminary structure-activity relationships indicated that the extension of 3-O-alkyl side chain resulted in a substantial improvement in the antibacterial activity, and the small group like methyl or ethyl group at the position 1–3 of the 3-O-alkyl side chain did not affect the antibacterial activity while the large group such as benzene or heterocycle at the position 4 or 5 of the 3-O-alkyl side chain could lead to poor antibacterial activity.