Design, synthesis and biological activity evaluation of novel 2, 6-difluorobenzamide derivatives through FtsZ inhibition. Issue 4 (15th February 2017)

• Record Type: Journal Article
• Authors: Bi, Fangchao; Guo, Liwei; Wang, Yinhu; Venter, Henrietta; Semple, Susan J.; Liu, Fang; Ma, Shutao
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 4(2017)
• Page Start: 958
• Page End: 962
• Publication Date: 2017-02-15
• Subjects: Benzamide derivatives -- Design and synthesis -- FtsZ inhibition -- Biological activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.12.081
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: The 2, 6-difluorobenzamide derivative (17 ) bearing 3- O -flexible alkyl side chains exhibited modest in vitro antibacterial and cell division inhibitory activities, while the 3- O -rigid heteroaryl substituted derivative (25 ) showed weak antibacterial activity although it had very similar structure to previously discovered compound6g . Highlights: Novel 2, 6-difluorobenzamide derivatives were synthesized and evaluated. Some compounds showed potent activity against both susceptible and resistant strains. They exerted their effects by inhibition of bacterial cell division protein FtsZ. Replacing the benzothiazole with benzimidazole lost its antibacterial activity. Abstract: Novel series of 3-substituted 2, 6-difluorobenzamide derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their in vitro antibacterial activity against various phenotype of Gram-positive and Gram-negative bacteria, and their cell division inhibitory activity against three representative strains. As a result, 3-chloroalkoxy derivative7, 3-bromoalkoxy derivative12 and 3-alkyloxy derivative17 were found to exhibit the best antibacterial activity against Bacillus subtilis with MICs of 0.25–1 μg/mL, and good activity (MIC < 10 μg/mL) against both susceptible and resistant Staphylococcus aureus . Additionally, all the three compounds displayed potent cell division inhibitory activity with MIC values of below 1 μg/mL against Bacillus subtilis and Staphylococcus aureus .