An expedient synthesis of N-(1-(5-mercapto-4-((substituted benzylidene)amino)-4H-1,2,4-triazol-3-yl)-2-phenylethyl)benzamides as jack bean urease inhibitors and free radical scavengers: Kinetic mechanism and molecular docking studies

Chem Biol Drug Des. 2017 Nov;90(5):764-777. doi: 10.1111/cbdd.12998. Epub 2017 Jun 19.

Abstract

In this study, some new azomethine-triazole hybrids 5a-5l derived from N-benzoyl-L-phenylalanine were synthesized and characterized. The synthesized compounds showed first-rate, urease inhibition, and compounds 5c and 5e were found to be most effective inhibitors with 0.0137 ± 0.00082 μm and 0.0183 ± 0.00068 μm, respectively (thiourea 15.151 ± 1.27 μm). The kinetic mechanism of urease inhibition revealed the compounds 5c and 5e to be non-competitive inhibitors, whereas compounds 5d and 5j were found to be of mixed-type inhibitors. Docking studies also indicated better interaction patterns with urease enzyme. The results of enzyme inhibition, kinetic mechanism and molecular docking suggest that these compounds can serve as lead compounds in the design of more effective urease inhibitors.

Keywords: antioxidant activity; drug-design; kinetic mechanism; molecular docking; triazolyl benzamides; urease inhibitors.

MeSH terms

  • Benzamides / chemical synthesis
  • Benzamides / chemistry*
  • Benzamides / pharmacology*
  • Canavalia / drug effects
  • Canavalia / enzymology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Free Radical Scavengers / chemical synthesis
  • Free Radical Scavengers / chemistry*
  • Free Radical Scavengers / pharmacology*
  • Molecular Docking Simulation
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology
  • Urease / antagonists & inhibitors*
  • Urease / metabolism

Substances

  • Benzamides
  • Enzyme Inhibitors
  • Free Radical Scavengers
  • Triazoles
  • Urease