Hetarylcoumarins: Synthesis and biological evaluation as potent α-glucosidase inhibitors

Bioorg Chem. 2017 Aug:73:1-9. doi: 10.1016/j.bioorg.2017.05.009. Epub 2017 May 10.

Abstract

In search of better α-glucosidase inhibitors, a series of novel hetarylcoumarins (3a-3j) were designed and synthesized through a facile multicomponent route where p-toluenesulfonic acid (PTSA) was explored as an efficient catalyst. These new scaffolds were further evaluated for their α-glucosidase inhibition potentials. All the derivatives exhibited good to excellent results which were comparable or even better than of standard drug acarbose. Of these compounds, a dihalogenated compound 3f was found to be the most effective one with IC50: 2.53±0.002µM. Molecular docking has predicted the plausible binding interactions of compounds 3f, 3g and 3j with α-glucosidase.

Keywords: Antidiabetic agents; Coumarin; Imidazole; Molecular docking; α-Glucosidase inhibitors.

MeSH terms

  • Coumarins / chemical synthesis
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Dose-Response Relationship, Drug
  • Glycoside Hydrolase Inhibitors / chemical synthesis
  • Glycoside Hydrolase Inhibitors / chemistry
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Molecular Docking Simulation
  • Molecular Structure
  • Saccharomyces cerevisiae / enzymology*
  • Structure-Activity Relationship
  • alpha-Glucosidases / isolation & purification
  • alpha-Glucosidases / metabolism*

Substances

  • Coumarins
  • Glycoside Hydrolase Inhibitors
  • alpha-Glucosidases