Design and synthesis of novel pyridazine N-aryl acetamides: In-vitro evaluation of α-glucosidase inhibition, docking, and kinetic studies

Bioorg Chem. 2020 Sep:102:104071. doi: 10.1016/j.bioorg.2020.104071. Epub 2020 Jul 6.

Abstract

We herein applied the four step-synthetic route to prepare the pyridazine core attached to the various N-aryl acetamides. By this approach, a new series of pyridazine-based compounds were synthesized, characterized and evaluated for their activities against α-glucosidase enzyme. In-vitro α-glucosidase assay established that twelve compounds are more potent than acarbose. Compound 7a inhibited α-glucosidase with the IC50 value of 70.1 µM. The most potent compounds showed no cytotoxicity against HDF cell line. Molecular docking and kinetic studies were performed to determine the modes of interaction and inhibition, respectively.

Keywords: Antidiabetic drug; Glucosidase inhibitor; Lawesson’s reagent; Pyridazine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / pharmacology
  • Acetamides / therapeutic use*
  • Drug Design
  • Glycoside Hydrolase Inhibitors / chemical synthesis*
  • Glycoside Hydrolase Inhibitors / pharmacology
  • Glycoside Hydrolase Inhibitors / therapeutic use*
  • Humans
  • Kinetics
  • Molecular Docking Simulation / methods*
  • Molecular Structure
  • Structure-Activity Relationship
  • alpha-Glucosidases / metabolism*

Substances

  • Acetamides
  • Glycoside Hydrolase Inhibitors
  • alpha-Glucosidases