Developing a scaffold for urease inhibition based on benzothiazoles: Synthesis, docking analysis, and therapeutic potential


ÖZİL M. , Tuzcuoglu O., EMİRİK M. , BALTAŞ N.

ARCHIV DER PHARMAZIE, 2021 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2021
  • Doi Number: 10.1002/ardp.202100200
  • Title of Journal : ARCHIV DER PHARMAZIE
  • Keywords: benzothiazole, molecular docking, molecular dynamics simulation, structure-activity relationship (SAR), urease inhibition, BIOLOGICAL EVALUATION, EFFICIENT SYNTHESIS, AGENTS SYNTHESIS, DERIVATIVES, HETEROCYCLES, MOLECULES, POLYMER, ANALOGS

Abstract

The synthesis, in silico molecular docking, and in vitro urease inhibition studies of a novel series of benzothiazole derivatives are reported. The title compounds in the two series, namely, 2-({5-[(benzothiazol-2-ylthio)methyl]-1,3,4-oxadiazol-2-yl}thio)-1-(4-substituted-phenyl)ethan-1-one and 2-(benzothiazol-2-ylthio)-1-(4-substituted-phenyl)ethan-1-one oxime, were synthesized by the reaction of benzo[d]thiazole-2-thiol with different kinds of intermediates in several steps using both conventional and microwave techniques. All compounds were found to have an excellent degree of urease-inhibitory potential ranging between 16.16 +/- 0.54 and 105.32 +/- 2.10 mu M when compared with the standard inhibitor acetohydroxamic acid with IC50 = 320.70 +/- 4.24 mu M. The structure-activity relationship was established in detail. The binding interactions of the compounds with the enzyme were confirmed through molecular docking. Further, 100 -ns molecular dynamics simulations were performed to investigate the stability and structural perturbations experienced by the most potent compound over the urease active site.