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

Bioorganic & medicinal chemistry letters 2020 Apr 01

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A library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involved a bio-inspired Diels-Alder cycloaddition, followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1 and Bcl-2 proteins. In this series of cyclohexenyl chalcone analogues, six compounds behaved as dual Bcl-xL/Mcl-1 inhibitors in micromolar range and one exhibited sub-micromolar affinities toward Mcl-1 and Bcl-2. The most potent compounds evaluated on A549 and MCF7 cancer cell lines showed moderate cytotoxicities. Copyright © 2020 Elsevier Ltd. All rights reserved.

Citation

Shelly Gapil Tiamas, Florian Daressy, Alma Abou Samra, Jérome Bignon, Vincent Steinmetz, Marc Litaudon, Christophe Fourneau, Kok Hoong Leong, Azhar Ariffin, Khalijah Awang, Sandy Desrat, Fanny Roussi. Pro-apoptotic carboxamide analogues of natural fislatifolic acid targeting Mcl-1 and Bcl-2. Bioorganic & medicinal chemistry letters. 2020 Apr 01;30(7):127003