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

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journal contribution
posted on 2017-09-21, 12:56 authored by Carina Proença, Marisa Freitas, Daniela Ribeiro, Eduardo F. T. Oliveira, Joana L. C. Sousa, Sara M. Tomé, Maria J. Ramos, Artur M. S. Silva, Pedro A. Fernandes, Eduarda Fernandes

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.

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.

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