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

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...

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Bibliographic Details
Published in:Food and chemical toxicology 2018-01, Vol.111, p.474-481
Main Authors: Proença, Carina, Freitas, Marisa, Ribeiro, Daniela, Sousa, Joana L.C., Carvalho, Félix, Silva, Artur M.S., Fernandes, Pedro A., Fernandes, Eduarda
Format: Article
Language:English
Subjects:
Diabetes mellitus
Enzymatic inhibition type
Flavonoids
PTP1B inhibition
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Summary: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. [Display omitted] •The inhibitory activity of a panel of 36 flavonoids was tested in vitro against human PTP1B.•Several of the studied flavonoids were shown to be potent PTP1B inhibitors.•The structure/activity relationship was established for the studied flavonoids.•Flavonoid C13, a mixed type inhibitor, is a promising leading compound.
ISSN:0278-6915
1873-6351
DOI:10.1016/j.fct.2017.11.039