Martina Durcik (Author), Päivi Tammela (Author), Michaela Barančokova (Author), Tihomir Tomašić (Author), Janez Ilaš (Author), Danijel Kikelj (Author), Nace Zidar (Author)

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 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.

Keywords

DNA gyrase;GyrB;antibacterials;inhibitors;pyrrolamides;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FFA - Faculty of Pharmacy
UDC: 543.2/.9.057
COBISS: 4461681 Link will open in a new window
ISSN: 1860-7187
Views: 1016
Downloads: 662
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Other data

Secondary language: Slovenian
Type (COBISS): Article
Embargo end date (OpenAIRE): 2019-01-22
Pages: str. 186-198
Volume: ǂVol. ǂ13
Issue: ǂiss. ǂ2
Chronology: 2018
DOI: 10.1002/cmdc.201700549
ID: 11043211