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

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

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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.

    Original languageEnglish
    Article number127003
    JournalBioorganic and Medicinal Chemistry Letters
    Volume30
    Issue number7
    DOIs
    Publication statusPublished - Apr 1 2020

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Pharmaceutical Science
    • Drug Discovery
    • Clinical Biochemistry
    • Organic Chemistry

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