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

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

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.

• Jezik: Angleški jezik
• Ključne besede: DNA gyrase, GyrB, antibacterials, inhibitors, pyrrolamides
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2018
• Št. strani: Str. 186-198
• Številčenje: Vol. 13, iss. 2
• PID: 20.500.12556/RUL-106642
• UDK: 543.2/.9.057
• ISSN pri članku: 1860-7187
• DOI: 10.1002/cmdc.201700549
• COBISS.SI-ID: 4461681
• Datum objave v RUL: 09.03.2019

Gradivo je del revije

• Naslov: ChemMedChem
• Skrajšan naslov: ChemMedChem
• Založnik: Wiley-VCH-Verl..
• ISSN: 1860-7187
• COBISS.SI-ID: 519053337