Inhibitory activity of (-)-epicatechin-3,5-O-digallate on α-glucosidase and in silico analysis

Int J Biol Macromol. 2018 Feb;107(Pt A):1162-1167. doi: 10.1016/j.ijbiomac.2017.09.091. Epub 2017 Sep 25.

Abstract

(-)-Epicatechin-3,5-O-digallate (ECDG) from Orostachys japonicus A. Berger was examined for inhibitory activity on α-glucosidase. The results showed that the IC50 value was achieved with nanomolar concentrations. Through the enzyme kinetic analysis, ECDG was shown to act as a competitive inhibitor of α-glucosidase by binding to the receptor active site. Fluorescence-quenching measurements showed that ECDG and the enzyme may have a one-to-one reaction with low quenching (Ksv) and binding constants. A molecular docking study was performed to evaluate the receptor-ligand complex. Asn236 was found to be particularly important for hydrogen bond formation during the molecular dynamics simulation.

Keywords: Competitive inhibitor; Epicatechin derivative; Molecular docking; Molecular dynamics; α-Glucosidase.

MeSH terms

  • Binding Sites
  • Catechin / analogs & derivatives*
  • Catechin / chemistry
  • Catechin / pharmacology
  • Computer Simulation
  • Crassulaceae / enzymology*
  • Glycoside Hydrolase Inhibitors / chemistry*
  • Glycoside Hydrolase Inhibitors / pharmacology
  • Hydrogen Bonding
  • Kinetics
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Protein Conformation
  • alpha-Glucosidases / chemistry*

Substances

  • Glycoside Hydrolase Inhibitors
  • Catechin
  • epicatechin gallate
  • alpha-Glucosidases