Pro-apoptotic carboxamide analogues of natural fislatifolic acid targeting Mcl-1 and Bcl-2. Issue 7 (1st April 2020)

• Record Type: Journal Article
• Authors: Gapil Tiamas, Shelly; Daressy, Florian; Abou Samra, Alma; Bignon, Jérome; Steinmetz, Vincent; Litaudon, Marc; Fourneau, Christophe; Hoong Leong, Kok; Ariffin, Azhar; Awang, Khalijah; Desrat, Sandy; Roussi, Fanny
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 7(2020)
• Publication Date: 2020-04-01
• Subjects: Natural product -- Diels-Alder -- Carboxamide -- Pro-apoptotic -- Mcl-1; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127003
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.