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 (avtor), Mirt, Matic (avtor), Barančokova, Michaela (avtor), Ilaš, Janez (avtor), Zidar, Nace (avtor), Tammela, Päivi (avtor), Kikelj, Danijel (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: antibacterial, DNA gyrase, docking, inhibitor, thiazole
• Vrsta gradiva: Znanstveno delo
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Recenzirani rokopis
• Leto izida: 2017
• Št. strani: Str. 338-349
• Številčenje: Vol. 25, iss. 1
• PID: 20.500.12556/RUL-106639
• UDK: 543:615.015.8
• ISSN pri članku: 0968-0896
• DOI: 10.1016/j.bmc.2016.10.038
• COBISS.SI-ID: 4240753
• Datum objave v RUL: 09.03.2019

Gradivo je del revije

• Naslov: Bioorganic & medicinal chemistry
• Skrajšan naslov: Bioorg. med. chem.
• Založnik: Elsevier
• ISSN: 0968-0896
• COBISS.SI-ID: 756527

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.
• Začetek licenciranja: 09.03.2019

Projekti

• Financer: EC - European Commission
• Program financ.: H2020
• Številka projekta: 642620
• Naslov: Interdisciplinary Training Network for Validation of Gram-Negative Antibacterial Targets
• Akronim: INTEGRATE