Synthesis, in-vitro evaluation, molecular docking, and kinetic studies of pyridazine-triazole hybrid system as novel α-glucosidase inhibitors

Bioorg Chem. 2021 Apr:109:104670. doi: 10.1016/j.bioorg.2021.104670. Epub 2021 Feb 1.

Abstract

In this study, we reported the discovery of pyridazine based 1,2,3-triazole derivatives as inhibitors of α-glucosidase. All target compounds exhibited significant inhibitory activities against yeast and rat α-glucosidase enzymes compared to positive control, acarbose. The most potent compound 6j, ethyl 3-(2-(1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)ethyl)-5,6-diphenylpyridazine-4-carboxylate exhibited IC50 values of 58, and 73 µM. Docking studies indicated the responsibility of hydrophobic and hydrogen bonding interactions in the ligand-enzyme complex stability. The in-vitro safety against the normal cell line was observed by toxicity evaluation of the selected compounds.

Keywords: Anti-diabetic drug; Click reaction; Pyridazine; Triazole; α-Glucosidase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line
  • Drug Design
  • Glycoside Hydrolase Inhibitors / chemistry
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Protein Binding
  • Protein Conformation
  • Pyridazines / chemistry
  • Pyridazines / pharmacology*
  • Saccharomyces cerevisiae / enzymology
  • Structure-Activity Relationship
  • Triazoles / chemistry
  • Triazoles / pharmacology*
  • alpha-Glucosidases / metabolism

Substances

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