Inhibition of protein tyrosine phosphatase 1B by flavonoids: A structure activity relationship study

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Proenca, C (Author) Other; Freitas, M (Author) Other; Ribeiro, D (Author) Other; Sousa, JLC (Author) Other; Felix Carvalho (Author) FFUP; Silva, AMS (Author) Other; Pedro A Fernandes (Author) FCUP; Eduarda Fernandes (Author) FFUP

Journal

Title: Food and Chemical Toxicology

Vol. 111

Pages: 474-481

ISSN: 0278-6915

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 38 Citations

Scopus - 40 Citations

Other information

Authenticus ID: P-00N-ADK

DOI: 10.1016/j.fct.2017.11.039

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8