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

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.

Graphical Abstract

Keywords:

• Diabetes
• flavonoids
• α-glucosidase inhibition
• in vitro
• in silico

Disclosure statement

The authors report no conflicts of interest.

Additional information

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.