Synthesis and antiproliferative activity of α-branched α,β-unsaturated ketones

A series of α-branched α,β-unsaturated ketones were prepared in a straightforward manner by the acid catalyzed coupling between arylalkynes and carbaldehydes. The method also allows producing as side product chalcone analogs bearing an additional α,β-unsaturated arylketone in the molecular scaffold. The evaluation of the antiproliferative activity in the human solid tumor cell lines HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D (breast) and WiDr (colon) provided a structure-activity relationship. Overall, the compounds presented active against the resistant Cancer cells T-47D. The resulting lead, displaying an unprecedented chalcone scaffold, showed GI50 values in the range 0.32-0.53 μM against all cell lines tested. The methoxy group present in the lead might play an important role in the activity.

Antitumor agents; Chalcones; Lewis acids; Structure–activity relationships; α-Branched α,β-unsaturated ketones.