Pro-apoptotic carboxamide analogues of natural fislatifolic acid targeting Mcl-1 and Bcl-2

International audience; A library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involve dabio-inspired Diels-Aldercycloaddition,followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1andBcl-2 proteins. In this series of cyclohexenyl chalcone analogues,six compounds behaved as dua lBcl-xL/Mcl-1 inhibitors in micromolar range and one exhibited sub-micromolar affinities toward Mcl-1andBcl-2.The most potent compounds evaluated on A549 and MCF7cancer cell lines showed moderate cytotoxicities