Durcik , M , Tammela , P S M , Barančoková , M , Tomašič , T , Ilaš , J , Kikelj , D & Zidar , N 2018 , ' Synthesis and Evaluation of N-Phenylpyrrolamides as DNA Gyrase B Inhibitors ' , ChemMedChem : chemistry enabling drug discovery. , vol. 13 , no. 2 , pp. 186-198 . https://doi.org/10.1002/cmdc.201700549
Title: | Synthesis and Evaluation of N-Phenylpyrrolamides as DNA Gyrase B Inhibitors |
Author: | Durcik, Martina; Tammela, Päivi Sirpa Marjaana; Barančoková, Michaela; Tomašič, Tihomir; Ilaš, Janez; Kikelj, Danijel; Zidar, Nace |
Contributor organization: | Faculty of Pharmacy Drug Research Program Division of Pharmaceutical Biosciences Bioactivity Screening Group |
Date: | 2018-01-22 |
Language: | eng |
Number of pages: | 13 |
Belongs to series: | ChemMedChem : chemistry enabling drug discovery. |
ISSN: | 1860-7179 |
DOI: | https://doi.org/10.1002/cmdc.201700549 |
URI: | http://hdl.handle.net/10138/313212 |
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 mu m against the Gram-positive Enterococcus faecalis. Some compounds displayed good antibacterial activities against an efflux-pump-deficient E.coli strain (MIC=6.25 mu m) and against wild-type E.coli in the presence of efflux pump inhibitor PA beta N (MIC=3.13 mu m). 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. |
Subject: |
317 Pharmacy
antibacterials DNA gyrase GyrB inhibitors pyrrolamides STRUCTURE-GUIDED DESIGN TOPOISOMERASE-IV PARE ANTIBACTERIAL ACTIVITY ATPASE INHIBITORS II TOPOISOMERASE BROAD-SPECTRUM PYRROLOPYRIMIDINE INHIBITORS PSEUDOMONAS-AERUGINOSA STAPHYLOCOCCUS-AUREUS ESCHERICHIA-COLI |
Peer reviewed: | Yes |
Usage restriction: | openAccess |
Self-archived version: | acceptedVersion |
Funder: | European Commission / Horizon 2020 SUOMEN AKATEMIA |
Grant number: | 642620 277001 |
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