Synthesis and biological evaluation of coumarin derivatives as α-glucosidase inhibitors

Eur J Med Chem. 2020 Mar 1:189:112013. doi: 10.1016/j.ejmech.2019.112013. Epub 2019 Dec 30.

Abstract

In this study, two series of coumarin derivatives 5a∼i and 6a∼i were synthesized, and their inhibitory activity against α-glucosidase was determined. The results indicated that most of the synthesized derivatives exhibited prominent inhibitory activities against α-glucosidase. Among them, compounds 5a and 5b showed the strongest inhibition with the IC50 values of 19.64 μM and 12.98 μM, respectively. Enzyme kinetic studies of compounds 5a and 5b proved that their inhibition was reversible and a mixed type. The KI and KIS values of compound 5a were calculated to be 27.39 μM and 13.02 μM, respectively, and the corresponding values for compound 5b being 27.02 μM and 13.65 μM, respectively. The docking studies showed that compound 5b could be inserted into the active pocket of α-glucosidase and form hydrogen bonds with LYS293 to enhance the binding affinity.

Keywords: Cinnamic acid; Coumarin; Enzyme inhibition; Molecular docking; Synthesis; α-Glucosidase.

Publication types

  • Evaluation Study

MeSH terms

  • Coumarins / chemistry*
  • Glycoside Hydrolase Inhibitors / chemical synthesis*
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Hydrogen Bonding
  • Kinetics
  • Molecular Docking Simulation
  • Molecular Structure
  • Structure-Activity Relationship
  • alpha-Glucosidases / chemistry*

Substances

  • Coumarins
  • Glycoside Hydrolase Inhibitors
  • alpha-Glucosidases