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

作者：Tomasic Tihomir^*; Mirt Matic; Barancokova Michaela; Ilas Janez; Zidar Nace; Tammela Paivi; Kikelj Danijel

来源：Bioorganic & Medicinal Chemistry, 2017, 25(1): 338-349.

DOI：10.1016/j.bmc.2016.10.038

• Antibacterial
• DNA gyrase
• Docking
• Inhibitor
• Thiazole

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.

• 出版日期2017-1-1