Chalcogen-containing phenolics as antiproliferative agents.

AIM: The increasing number of cancer cases has stimulated researchers to seek for novel approaches. We have combined two bioactive moieties: a polyphenolic scaffold and an organoselenium motif. Four different families (isothiocyanates/thioureas, and their selenium isosters) derived from dopamine, (±)-norepinephrine and R-epinephrine were accessed.

RESULTS: Heterocumulenes derived from dopamine and β-O-methylnoradrenaline were strong antiproliferative agents (GI50 <10 μM). Selenoureas derived from β-O-methylnoradrenaline bearing electron-withdrawing groups (halogen, -NO2 , -Ph) on the phenyl ring, were also strong antiproliferative agents, besides exhibiting good antiradical and glutathione peroxidase-like activities. Up to a 14-fold increased activity was achieved compared with classical chemotherapeutic agents, exhibiting also different mechanisms of action (cell cycle assays). Redox analysis on HeLa cells suggested an increase of ROS levels after the incubation period.

CONCLUSION: the combination of organoselenium and phenolic moieties might provide valuable lead compounds with relevant antiproliferative properties.