Design, synthesis and biological evaluation of 4,5-dibromo-N-(thiazol-2-yl)-1H-pyrrole-2-carboxamide derivatives as novel DNA gyrase inhibitors

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Tomašič , T , Mirt , M , Barančoková , M , Ilaš , J , Zidar , N , Tammela , P S M & Kikelj , D 2017 , ' Design, synthesis and biological evaluation of 4,5-dibromo- N -(thiazol-2-yl)-1 H -pyrrole-2-carboxamide derivatives as novel DNA gyrase inhibitors ' , Bioorganic & Medicinal Chemistry , vol. 25 , no. 1 , pp. 338-349 . https://doi.org/10.1016/j.bmc.2016.10.038

Title: Design, synthesis and biological evaluation of 4,5-dibromo-N-(thiazol-2-yl)-1H-pyrrole-2-carboxamide derivatives as novel DNA gyrase inhibitors
Author: Tomašič, Tihomir; Mirt, Matic; Barančoková, Michaela; Ilaš, Janez; Zidar, Nace; Tammela, Päivi Sirpa Marjaana; Kikelj, Danijel
Contributor: University of Helsinki, Faculty of Pharmacy
Date: 2017-01-01
Language: eng
Number of pages: 12
Belongs to series: Bioorganic & Medicinal Chemistry
ISSN: 0968-0896
URI: http://hdl.handle.net/10138/307687
Abstract: Development of novel DNA gyrase B inhibitors is an important field of antibacterial drug discovery whose aim is to introduce a more effective representative of this mechanistic class into the clinic. In the present study, two new series of Escherichia coli DNA gyrase inhibitors bearing the 4,5-dibromopyrrolamide moiety have been designed and synthesized. 4,5,6,7-Tetrahydrobenzo[1,2-d] thiazole-2,6-diamine derivatives inhibited E. coli DNA gyrase in the submicromolar to low micromolar range (IC50 values between 0.891 and 10.4 mu M). Their "ring-opened" analogues, based on the 2-(2-aminothiazol-4-yl) acetic acid scaffold, displayed weaker DNA gyrase inhibition with IC50 values between 15.9 and 169 mu M. Molecular docking experiments were conducted to study the binding modes of inhibitors. (C) 2016 Elsevier Ltd. All rights reserved.
Subject: 1182 Biochemistry, cell and molecular biology
317 Pharmacy
116 Chemical sciences
Antibacterial
DNA gyrase
Docking
Inhibitor
Thiazole
SODIUM-CHANNEL MODULATORS
IN-SILICO DISCOVERY
TOPOISOMERASE-IV
ANTIBACTERIAL AGENTS
MARINE ALKALOIDS
STAPHYLOCOCCUS-AUREUS
IIA TOPOISOMERASES
ATPASE DOMAINS
CLATHRODIN
ANALOGS
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