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

Pro-apoptotic carboxamide analogues of natural fislatifolic acid targeting Mcl-1 and Bcl-2.
Bioorg Med Chem Lett. 2020 Feb 03;:127003
Authors: Gapil Tiamas S, Daressy F, Abou Samra A, Bignon J, Steinmetz V, Litaudon M, Fourneau C, Hoong Leong K, Ariffin A, Awang K, Desrat S, Roussi F
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.
PMID: 32035700 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry Letters - February 2, 2020 Category: Chemistry Authors: Gapil Tiamas S, Daressy F, Abou Samra A, Bignon J, Steinmetz V, Litaudon M, Fourneau C, Hoong Leong K, Ariffin A, Awang K, Desrat S, Roussi F Tags: Bioorg Med Chem Lett Source Type: research