Design, synthesis and biological evaluation of biphenyl-benzamides as potent FtsZ inhibitors

In this study, a series of novel biphenyl-benzamides as FtsZ inhibitors has been rationally designed, synthesized and evaluated for their antibacterial activities against various Gram-positive bacteria strains. In particular, the most promising compound 30 exhibited excellent antibacterial activities, especially against four different Bacillus subtilis strains, with an MIC range of 0.008 μg/mL to 0.063 μg/mL. Moreover, compound 30 also showed good pharmaceutical properties with low cytotoxicity (CC50 > 20 μg/mL), excellent human metabolic stability (T1/2 = 111.98 min), moderate pharmacokinetics (T1/2 = 2.26 h, F = 61.2%) and in vivo efficacy, which can be identified as a promising FtsZ inhibitor worthy of further profiling.PMID:35763867 | DOI:10.1016/j.ejmech.2022.114553
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Source Type: research