Synthesis and evaluation of N-phenylpyrrolamides as DNA gyrase B inhibitorsDurcik, Martina (Avtor) Tammela, Päivi (Avtor) Barančokova, Michaela (Avtor) Tomašič, Tihomir (Avtor) Ilaš, Janez (Avtor) Kikelj, Danijel (Avtor) Zidar, Nace (Avtor) DNA gyraseGyrBantibacterialsinhibitorspyrrolamidesATP-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 47micro nm against E.coli DNA gyrase, and a minimum inhibitory concentration (MIC) of 12.5 microm against the Gram-positive Enterococcus faecalis. Some compounds displayed good antibacterial activities against an efflux-pump-deficient E. coli strain (MIC=6.25 microm) and against wild-type E. coli in the presence of efflux pump inhibitor PAbetaN (MIC=3.13 microm). 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.20182019-03-09 19:46:20Članek v reviji106642sl