Synthesis and biological evaluation of novel 2,4,5-triarylimidazole-1,2,3-triazole derivatives via click chemistry as α-glucosidase inhibitors

Bioorg Med Chem Lett. 2016 Dec 1;26(23):5719-5723. doi: 10.1016/j.bmcl.2016.10.057. Epub 2016 Oct 21.

Abstract

A novel series of 2,4,5-triarylimidazole-1,2,3-triazole derivatives were synthesized via copper(I)-catalyzed azide-alkyne click chemistry, and evaluated for their α-glucosidase inhibitory activity. All tested compounds showed potent α-glucosidase inhibitory activity with IC50 ranging from 15.16±0.18 to 48.15±0.37μM, in comparison to the standard drug, acarbose (IC50=817.38±6.27μM). Among all the tested compounds, 5j was found to be the most active compound with IC50 value of 15.16±0.18μM and behaved as a noncompetitive inhibitor with a Ki of 14.78μM. In addition, molecular docking study was carried out to explore the binding interactions of these compounds with α-glucosidase enzyme.

Keywords: 1,2,3-Triazole; 2,4,5-Triarylimidazole; Click chemistry; Enzyme kinetic study; Molecular docking; α-Glucosidase inhibitor.

MeSH terms

  • Click Chemistry
  • Glycoside Hydrolase Inhibitors / chemical synthesis
  • Glycoside Hydrolase Inhibitors / chemistry*
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Molecular Docking Simulation
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / metabolism
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacology*
  • alpha-Glucosidases / metabolism*

Substances

  • Glycoside Hydrolase Inhibitors
  • Imidazoles
  • Triazoles
  • alpha-Glucosidases