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

Published on Feb 3, 2020in Bioorganic & Medicinal Chemistry Letters2.448
· DOI :10.1016/J.BMCL.2020.127003
Shelly Gapil Tiamas (UM: University of Malaya), Florian Daressy (Institut de Chimie des Substances Naturelles)+ 9 AuthorsKhalijah Awang29
Estimated H-index: 29
(UM: University of Malaya)
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.
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