Synthesis, Biological Evaluation and in Silico Studies of New Pyrazoline Derivatives Bearing Benzo[d]thiazol-2(3H)-one Moiety as Potential Urease Inhibitors


CHEMISTRY & BIODIVERSITY, 2022 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2022
  • Doi Number: 10.1002/cbdv.202100826
  • Title of Journal : CHEMISTRY & BIODIVERSITY
  • Keywords: urease enzyme, pyrazoline, molecular docking, molecular dynamic simulations, ADME, CRYSTAL-STRUCTURE, FORCE-FIELD, DOCKING, VITRO


Novel pyrazoline derivatives containing benzo[d]thiazol-2(3H)-one moiety were synthesized and screened for their inhibitory properties against urease, a clinically important metabolic enzyme. In vitro enzyme inhibition studies revealed that all pyrazolines (7.21-87.77 mu M) were more potent than the standard inhibitor acetohydroxamic acid (251.74 mu M) against the urease enzyme. Most notably, compound 2m, which is more active than the other compounds in vitro and molecular docking studies, showed a significant inhibition potential and efficient IC50 values (7.21 +/- 0.09 mu M) and in silico inhibition constant (0.11 mu M). Furthermore, molecular dynamics (MD) simulation analysis suggests that the binding stability of urease enzyme and compound 2m were stably maintained during the 100 ns simulation time. Compound 2m also exhibited good physicochemical and pharmacokinetic parameters. The overall results of urease inhibition have indicated that these pyrazoline derivative compounds can be further optimized and developed for the discovery of novel urease inhibitors.