Design, synthesis and biological evaluation of 4,5-dibromo-N-(thiazol-2-yl)-1H-pyrrole-2-carboxamide derivatives as novel DNA gyrase inhibitorsTomašič, Tihomir (Avtor) Mirt, Matic (Avtor) Barančokova, Michaela (Avtor) Ilaš, Janez (Avtor) Zidar, Nace (Avtor) Tammela, Päivi (Avtor) Kikelj, Danijel (Avtor) antibacterialDNA gyrasedockinginhibitorthiazoleDevelopment 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.20172019-03-09 19:16:43Znanstveno delo106639sl