Evaluation of synthetic aminoquinoline derivatives as urease inhibitors: in vitro, in silico and kinetic studies

Future Med Chem. 2023 Sep;15(18):1703-1717. doi: 10.4155/fmc-2023-0168. Epub 2023 Oct 10.

Abstract

Background: Quinoline and acyl thiourea scaffolds have major chemical significance in medicinal chemistry. Quinoline-based acyl thiourea derivatives may potentially target the urease enzyme. Materials & methods: Quinoline-based acyl thiourea derivatives 1-26 were synthesized and tested for urease inhibitory activity. Results: 19 derivatives (1-19) showed enhanced urease enzyme inhibitory potential (IC50 = 1.19-18.92 μM) compared with standard thiourea (IC50 = 19.53 ± 0.032 μM), whereas compounds 20-26 were inactive. Compounds with OCH3, OC2H5, Br and CH3 on the aryl ring showed significantly greater inhibitory potential than compounds with hydrocarbon chains of varying length. Molecular docking studies were conducted to investigate ligand interactions with the enzyme's active site. Conclusion: The identified hits can serve as potential leads against the drug target urease in advanced studies.

Keywords: acyl thiourea derivatives; in silico studies; in vitro studies; quinoline; urease inhibition.

MeSH terms

  • Aminoquinolines
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / pharmacology
  • Kinetics
  • Molecular Docking Simulation
  • Molecular Structure
  • Quinolines* / pharmacology
  • Structure-Activity Relationship
  • Thiourea / chemistry
  • Thiourea / pharmacology
  • Urease / chemistry
  • Urease / metabolism

Substances

  • Enzyme Inhibitors
  • Urease
  • Thiourea
  • Aminoquinolines
  • Quinolines