α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure-activity relationship study

J Enzyme Inhib Med Chem. 2017 Dec;32(1):1216-1228. doi: 10.1080/14756366.2017.1368503.

Abstract

α-Glucosidase inhibitors are described as the most effective in reducing post-prandial hyperglycaemia (PPHG) from all available anti-diabetic drugs used in the management of type 2 diabetes mellitus. As flavonoids are promising modulators of this enzyme's activity, a panel of 44 flavonoids, organised in five groups, was screened for their inhibitory activity of α-glucosidase, based on in vitro structure-activity relationship studies. Inhibitory kinetic analysis and molecular docking calculations were also applied for selected compounds. A flavonoid with two catechol groups in A- and B-rings, together with a 3-OH group at C-ring, was the most active, presenting an IC50 much lower than the one found for the most widely prescribed α-glucosidase inhibitor, acarbose. The present work suggests that several of the studied flavonoids have the potential to be used as alternatives for the regulation of PPHG.

Keywords: Diabetes; flavonoids; in silico; in vitro; α-glucosidase inhibition.

MeSH terms

  • Acarbose / chemistry
  • Acarbose / pharmacology
  • Computer Simulation*
  • Dose-Response Relationship, Drug
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Glycoside Hydrolase Inhibitors / chemistry*
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Molecular Docking Simulation*
  • Molecular Structure
  • Saccharomyces cerevisiae / enzymology
  • Structure-Activity Relationship
  • alpha-Glucosidases / metabolism*

Substances

  • Flavonoids
  • Glycoside Hydrolase Inhibitors
  • alpha-Glucosidases
  • Acarbose

Grants and funding

The authors acknowledge the financial support from National funds [Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência (FCT/MEC)] and European Union funds [Fundo Europeu de Desenvolvimento Regional (FEDER)] under the program PT2020 (PT2020 UID/MULTI/04378/2013 - POCI/01/0145/FEDER/007728), the framework of QREN (NORTE-01-0145-FEDER-000024), and Programa Operacional Competitividade e Internacionalização (COMPETE). Carina Proença acknowledges FCT the financial support for the PhD grant (SFRH/BD/116005/2016), in the ambit of “QREN - POPH - Tipologia 4.1 - Formação Avançada”, co-sponsored by Fundo Social Europeu (FSE) and by national funds of Ministério da Ciência, Tecnologia e Ensino Superior (MCTES). Daniela Ribeiro acknowledges FEDER, through COMPETE and FCT, the financial support for the Post-doc grant in the ambit of the project PTDC/QEQ-QAN/1742/2014 - POCI-01-0145-FEDER-016530.