Novel Resveratrol Analogues: Synthesis, Metabolism and Cell Proliferation

Resveratrol or trans-3,4’,5-trihydroxystilbene is a naturally occurring phytochemical contained in red grapes skin, nuts and berries. It has been shown over the years to have different biological properties particularly in the chemoprevention of cancer. However, it is metabolised in vivo to sulfates and glucuronides within 1h and is active against different targets in a dose dependant manner. A library of new analogues of resveratrol has been synthesised with the aim of stopping or at least slowing down the metabolism whilst keeping its activity on the inhibition of cancer cell proliferation. Seven new analogues of resveratrol were synthesised in which the phenol substituents were systematically replaced by benzylic alcohols and/or methoxy groups. The library was then assessed in in vitro enzymatic metabolism with mouse and human liver fractions in the presence of a cofactor. The compounds were also evaluated as inhibitors of HCA-7 colorectal cancer cell proliferation.