Molecular structure-function relationship of dietary polyphenols for inhibiting VEGF-induced VEGFR-2 activity.

ABSTRACT:

Scope

We recently reported potent inhibition of VEGF signalling by two flavanols at sub-micromolar concentrations, mediated by direct binding of the flavanols to VEGF. The aim of this study was to quantify the inhibitory potency and binding affinity of a wide range of dietary polyphenols and determine the structural requirements for VEGF inhibition.

Methods and results

The concentration of polyphenol required to cause 50% inhibition (IC50 ) of VEGF-dependent VEGFR-2 activation in HUVECS was determined after pretreating VEGF with polyphenols at various concentations. Binding affinities and binding sites on VEGF were predicted using in-silico modelling. Ellagic acid and 15 flavonoids had IC50 values ≤10 μM while 28 other polyhenols were weak/non-inhibitors. Structural features

SUBMITTER: Cerezo AB 

PROVIDER: S-EPMC4973850 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature