Structure and cytotoxic activity of terpenoid-like chalcones

Abstract

Compounds with either ionone or chalcone skeletons present many biological properties including anticancer activity. Here we have prepared eight terpenoid-like chalcones in order to assess whether hybrid compounds with both structural frameworks could exhibit enhanced pharmacological profile. The terpenoid-like chalcones were synthesized by means of Claisen–Schmidt condensation reaction, using either α- or β-ionone with substituted benzaldehydes. The structure of six derivatives was elucidated by single crystal X-ray diffraction technique for the first time. Cyclohexene ring adopts half-chair conformation in α-ionone-derived chalcone with quaternary carbon at the flap, while twist puckering was observed in β-ionone terpenoid-like chalcones. All prepared compounds were tested for their cytotoxic activity against three cancer cell lines, namely SF-295, HCT-116 and OVCAR-8, which allowed us to establish some structure–activity relationships. Terpenoid-like chalcones with nitro substituted phenyl rings, regardless of its position and ionone type, were the most active chalcones among all that tested. The IC50 values do also reveal a trend of decrease in cytotoxic activity with weak electron-withdrawing groups at phenyl ring.