Synthesis of novel N-(1,3-thiazol-2-yl)benzamide clubbed oxadiazole scaffolds: Urease inhibition, Lipinski rule and molecular docking analyses

Bioorg Chem. 2019 Mar:83:63-75. doi: 10.1016/j.bioorg.2018.10.018. Epub 2018 Oct 12.

Abstract

Present work aimed to synthesize some unique bi-heterocyclic benzamides as lead compounds for the in vitro inhibition of urease enzyme, followed by in silico studies. These targeted benzamides were synthesized in good yields through a multi-step protocol and their structures were confirmed by IR, 1H NMR, 13C NMR, EI-MS and elemental analysis. The in vitro screening results showed that most of the ligands exhibited good inhibitory potentials against the urease. Chemo-informatics analysis envisaged that all these compounds obeyed the Lipinski's rule. Molecular docking results showed that 7h exhibited good binding energy value (-8.40 kcal/mol) and was bound within the active region of urease enzyme. From the present investigation, it was inferred that some of these potent urease inhibitors might serve as novel templates in drug designing.

Keywords: Benzamides; Bi-heterocycles; Molecular docking; Oxadiazole; Thiazole; Urease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Canavalia / enzymology
  • Dose-Response Relationship, Drug
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Ligands
  • Molecular Docking Simulation*
  • Molecular Structure
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology*
  • Structure-Activity Relationship
  • Urease / antagonists & inhibitors*
  • Urease / metabolism

Substances

  • Enzyme Inhibitors
  • Ligands
  • Oxadiazoles
  • Urease