abstract
alpha-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 alpha-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 alpha-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
TYPE-2 DIABETES-MELLITUS; POSTPRANDIAL HYPERGLYCEMIA; ENZYME-INHIBITION; HUMAN NEUTROPHILS; SCORING FUNCTION; DOCKING; AMYLASE; MECHANISM; KINETICS; APIGENIN
subject category
Biochemistry & Molecular Biology; Pharmacology & Pharmacy
authors
Proenca, C; Freitas, M; Ribeiro, D; Oliveira, EFT; Sousa, JLC; Tome, SM; Ramos, MJ; Silva, AMS; Fernandes, PA; Fernandes, E
our authors
Joana Lia Cardoso de Sousa
Post-Doc Fellowshipacknowledgements
The authors acknowledge the financial support from National funds [Fundacao para a Ciencia e Tecnologia and Ministerio da Educacao e Ciencia (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 Internacionalizacao (COMPETE). Carina Proenca acknowledges FCT the financial support for the PhD grant (SFRH/BD/116005/2016), in the ambit of "QREN - POPH - Tipologia 4.1 - Formacao Avancada", co-sponsored by Fundo Social Europeu (FSE) and by national funds of Ministerio da Ciencia, 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.