Imidazole analogues of resveratrol: synthesis and cancer cell growth evaluation

Novel trans-restricted analogues of resveratrol in which the C-C double bond of the natural derivative has been replaced by diaryl substituted imidazole analogues have been designed. The syntheses of 1,4-, 2,4-, and 2,5-diarylimidazoles, in which the two aryl moieties are linked to the heteroaromatic core in a 1,3 fashion in order to preserve the trans stereochemistry, have been successfully carried out by regioselective sequential transition metal-catalyzed arylations of simple, commercially available imidazole precursors. The anticancer activity of selected analogues has been evaluated in vitro against the NCI-60 human tumor cell lines panel. From this screening, we were able to select a synthetic candidate that resulted more active than its natural lead.