New N-phenylpyrrolamide inhibitors of DNA gyrase with improved antibacterial activity.

ABSTRACT: This study presents the discovery of a new series of N-phenylpyrrolamide inhibitors of bacterial DNA gyrase with improved antibacterial activity. The most potent inhibitors had low nanomolar IC₅₀ values against Escherichia coli DNA gyrase (IC₅₀; 2-20 nM) and E. coli topoisomerase IV (22i, IC₅₀ = 143 nM). Importantly, none of the compounds showed activity against human DNA topoisomerase IIα, indicating selectivity for bacterial targets. Among the tested compounds, 22e emerged as the most effective against Gram-positive bacteria with minimum inhibitory concentration (MIC) values of 0.25 μg mL^-1 against Staphylococcus aureus ATCC 29213 and MRSA, and 0.125 μg mL^-1 against Enterococcus faecalis ATCC 29212.

SUBMITTER: Cotman AE 

PROVIDER: S-EPMC11378028 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature