Synthesis, in vitro evaluation and molecular docking studies of novel triazine-triazole derivatives as potential α-glucosidase inhibitors

Eur J Med Chem. 2017 Jan 5:125:423-429. doi: 10.1016/j.ejmech.2016.09.067. Epub 2016 Sep 21.

Abstract

A novel series of triazine-triazole derivatives 7a-7m were synthesized, characterized by 1H NMR and evaluated for their α-glucosidase inhibitory activity. All the synthesized compounds displayed potent α-glucosidase inhibitory activity with IC50 range of 11.63 ± 0.15 to 37.44 ± 0.35 μM, when compared to the standard drug acarbose (IC50 = 817.38 ± 6.27 μM). Among the series, compound 7i (IC50 = 11.63 ± 0.15 μM) bearing 2,5-dichloro substitution at phenyl ring, represented the most potent α-glucosidase inhibitory activity. Molecular docking studies of the most active compounds with the homology modelled α-glucosidase were also performed to explore the possible inhibitory mechanism. Our studies shown that these triazine-triazole derivatives are a new class of α-glucosidase inhibitors.

Keywords: 1,2,3-Triazole; 1,2,4-Triazine; Click chemistry; Molecular docking; α-Glucosidase inhibitor.

MeSH terms

  • Click Chemistry
  • Drug Design
  • Glycoside Hydrolase Inhibitors / chemical synthesis
  • Glycoside Hydrolase Inhibitors / chemistry*
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Humans
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Molecular Docking Simulation
  • Structure-Activity Relationship
  • Triazines / chemical synthesis
  • Triazines / chemistry*
  • Triazines / pharmacology*
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacology*
  • alpha-Glucosidases / metabolism

Substances

  • Glycoside Hydrolase Inhibitors
  • Hypoglycemic Agents
  • Triazines
  • Triazoles
  • alpha-Glucosidases