RRC ID 55803
著者 Durcik M, Tammela P, Barančoková M, Tomašič T, Ilaš J, Kikelj D, Zidar N.
タイトル Synthesis and Evaluation of N-Phenylpyrrolamides as DNA Gyrase B Inhibitors.
ジャーナル 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.
巻・号 13(2)
ページ 186-198
公開日 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
引用数 12
リソース情報
原核生物(大腸菌) JW5503, JD17464