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

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

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 microM). 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 microM. Molecular docking experiments were conducted to study the binding modes of inhibitors.

• Language: English
• Keywords: antibacterial, DNA gyrase, docking, inhibitor, thiazole
• Work type: Scientific work
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Author Accepted Manuscript
• Year: 2017
• Number of pages: Str. 338-349
• Numbering: Vol. 25, iss. 1
• PID: 20.500.12556/RUL-106639
• UDC: 543:615.015.8
• ISSN on article: 0968-0896
• DOI: 10.1016/j.bmc.2016.10.038
• COBISS.SI-ID: 4240753
• Publication date in RUL: 09.03.2019

Record is a part of a journal

• Title: Bioorganic & medicinal chemistry
• Shortened title: Bioorg. med. chem.
• Publisher: Elsevier
• ISSN: 0968-0896
• COBISS.SI-ID: 756527

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
• Licensing start date: 09.03.2019

Projects

• Funder: EC - European Commission
• Funding programme: H2020
• Project number: 642620
• Name: Interdisciplinary Training Network for Validation of Gram-Negative Antibacterial Targets
• Acronym: INTEGRATE