abstract
The classical non-transmembrane protein tyrosine phosphatase 1B (PTP1B) has emerged as a key negative regulator of insulin signaling pathways that leads to insulin resistance, turning this enzyme a promising therapeutic target in the management of type 2 diabetes mellitus (T2DM). In the present work, the in vitro inhibitory activity of a panel of structurally related flavonoids, for recombinant human PTP1B was studied and the type of inhibition of the most active compounds further evaluated. The majority of the studied flavonoids was tested in this work for the first time, including flavonoid C13, which was the most potent inhibitor. It was observed that the ability to inhibit PTP1B depends on the nature, position and number of substituents in the flavonoid structure, as the presence of both 7- and 8-OBn groups in the A ring, together with the presence of both 3' and 4'-OMe groups in the B ring and the 3-OH group in the C ring; these substituents increase the flavonoids' ability to inhibit PTP1B. In conclusion, some of the tested flavonoids seem to be promising PTP1B inhibitors and potential effective agents in the management of T2DM, by increasing insulin sensitivity.
keywords
ANTI-ALZHEIMERS DISEASE; PTP1B INHIBITORS; C-GLYCOSYLATION; GLUCOSE-UPTAKE; OBESITY; MODULATION; TARGET; MICE
subject category
Food Science & Technology; Toxicology
authors
Proenca, C; Freitas, M; Ribeiro, D; Sousa, JLC; Carvalho, F; 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; QOPNA research unit FCT UID/QUI/00062/2013), the framework of QREN (NORTE-01-0145-FEDER-000024), and Programa Operacional Competitividade e Internacionalizacao (COMPETE) (PTDC/QEQ-QAN/ 1742/2014 - POCI-01-0145-FEDER-016530). 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).