Synthesis and evaluation of N-phenylpyrrolamides as DNA gyrase B inhibitors

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

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.

• Language: English
• Keywords: DNA gyrase, GyrB, antibacterials, inhibitors, pyrrolamides
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2018
• Number of pages: Str. 186-198
• Numbering: Vol. 13, iss. 2
• PID: 20.500.12556/RUL-106642
• UDC: 543.2/.9.057
• ISSN on article: 1860-7187
• DOI: 10.1002/cmdc.201700549
• COBISS.SI-ID: 4461681
• Publication date in RUL: 09.03.2019

Record is a part of a journal

• Title: ChemMedChem
• Shortened title: ChemMedChem
• Publisher: Wiley-VCH-Verl..
• ISSN: 1860-7187
• COBISS.SI-ID: 519053337