RRC ID 55803
Author Durcik M, Tammela P, Barančoková M, Tomašič T, Ilaš J, Kikelj D, Zidar N.
Title Synthesis and Evaluation of N-Phenylpyrrolamides as DNA Gyrase B Inhibitors.
Journal ChemMedChem
Abstract ATP-competitive inhibitors of DNA gyrase and topoisomerase IV are among the most interesting classes of antibacterial drugs that are unrepresented in the antibacterial pipeline. We developed 32 new N-phenylpyrrolamides and evaluated them against DNA gyrase and topoisomerase IV from E. coli and Staphylococcus aureus. Antibacterial activities were studied against Gram-positive and Gram-negative bacterial strains. The most potent compound displayed an IC50 of 47 nm against E. coli DNA gyrase, and a minimum inhibitory concentration (MIC) of 12.5 μm against the Gram-positive Enterococcus faecalis. Some compounds displayed good antibacterial activities against an efflux-pump-deficient E. coli strain (MIC=6.25 μm) and against wild-type E. coli in the presence of efflux pump inhibitor PAβN (MIC=3.13 μm). Here we describe new findings regarding the structure-activity relationships of N-phenylpyrrolamide DNA gyrase B inhibitors and investigate the factors that are important for the antibacterial activity of this class of compounds.
Volume 13(2)
Pages 186-198
Published 2018-1-22
DOI 10.1002/cmdc.201700549
PMID 29206345
MeSH Amides / chemical synthesis* Amides / pharmacology Anti-Bacterial Agents / chemical synthesis* Anti-Bacterial Agents / pharmacology Bacterial Proteins / antagonists & inhibitors* DNA Gyrase / metabolism* DNA Topoisomerase IV / antagonists & inhibitors* Escherichia coli / drug effects Escherichia coli / enzymology Gram-Positive Bacteria / drug effects Humans Microbial Sensitivity Tests Molecular Docking Simulation Protein Binding Protein Conformation Pyrroles / chemical synthesis* Pyrroles / pharmacology Staphylococcus aureus / enzymology Structure-Activity Relationship Topoisomerase II Inhibitors / chemical synthesis* Topoisomerase II Inhibitors / pharmacology
IF 3.016
Times Cited 12
Prokaryotes E. coli JW5503, JD17464