Evaluation of a flavonoids library for inhibition of pancreatic α-amylase towards a structure-activity relationship

Carina Proença; Marisa Freitas; Daniela Ribeiro; Sara M Tomé; Eduardo F T Oliveira; Matilde F Viegas; Alberto N Araújo; Maria J Ramos; Artur M S Silva; Pedro A Fernandes; Eduarda Fernandes

doi:10.1080/14756366.2018.1558221

Evaluation of a flavonoids library for inhibition of pancreatic α-amylase towards a structure-activity relationship

J Enzyme Inhib Med Chem. 2019 Dec;34(1):577-588. doi: 10.1080/14756366.2018.1558221.

Affiliations

¹ a LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy , University of Porto , Porto , Portugal.
² b Department of Chemistry and QOPNA , University of Aveiro , Aveiro , Portugal.
³ c UCIBIO, REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences , University of Porto , Porto , Portugal.

Abstract

α-Amylase has been considered an important therapeutic target for the management of type 2 diabetes mellitus (T2DM), decreasing postprandial hyperglycaemia (PPHG). In the present work, a panel of 40 structurally related flavonoids was tested, concerning their ability to inhibit α-amylase activity, using a microanalysis screening system, an inhibitory kinetic analysis and molecular docking calculations. From the obtained results, it was possible to observe that the flavone with a -Cl ion at 3-position of C-ring, an -OH group at 3'- and 4'- positions of B-ring and at 5- and 7- positions of A-ring and the C2 = C3 double bond, was the most active tested flavonoid, through competitive inhibition. In conclusion, some of the tested flavonoids have shown promising inhibition of α-amylase and may be considered as possible alternatives to the modulation of T2DM.

Keywords: diabetes; docking; flavonoids; α-Amylase inhibition.

MeSH terms

Dose-Response Relationship, Drug
Flavonoids / chemical synthesis
Flavonoids / chemistry
Flavonoids / pharmacology*
Glycoside Hydrolase Inhibitors / chemical synthesis
Glycoside Hydrolase Inhibitors / chemistry
Glycoside Hydrolase Inhibitors / pharmacology*
Humans
Molecular Structure
Pancreatic alpha-Amylases / antagonists & inhibitors*
Pancreatic alpha-Amylases / metabolism
Small Molecule Libraries / chemical synthesis
Small Molecule Libraries / chemistry
Small Molecule Libraries / pharmacology*
Structure-Activity Relationship

Substances

Flavonoids
Glycoside Hydrolase Inhibitors
Small Molecule Libraries
Pancreatic alpha-Amylases

Grants and funding

This work was financed by FEDER–Fundo Europeu de Desenvolvimento Regional through the COMPETE 2020–Operacional Programme for Competitiveness and Internationalisation (POCI), and by Portuguese funds through FCT–Fundação para a Ciência e a Tecnologia in the framework of the project POCI-01–0145-FEDER-029241. Carina Proença acknowledges FCT the financial support for the PhD grant [SFRH/BD/116005/2016], in the ambit of "QREN–POPH–Tipologia 4.1–FormaçãoAvançada", co-sponsored by Fundo Social Europeu (FSE) and by national funds of Ministério da Ciência, Tecnologia e Ensino Superior (MCTES).