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ID: ALA3351486

Journal: Bioorg Med Chem Lett

Title: Pro-apoptotic meiogynin A derivatives that target Bcl-xL and Mcl-1.

Authors: Desrat S, Pujals A, Colas C, Dardenne J, Gény C, Favre L, Dumontet V, Iorga BI, Litaudon M, Raphaël M, Wiels J, Roussi F.

Abstract: The biological evaluation of a natural sesquiterpene dimer meiogynin A 1, is described as well as that of five non-natural analogues. Although active on a micromolar range on the inhibition of Bcl-xL/Bak and Mcl-1/Bid interaction, meiogynin A 1 is not cytotoxic on three cell lines that overexpress Bcl-xL and Mcl-1. Contrarily, one of its analogues 6 with an inverted configuration on the side chain and an aromatic moiety replacing the cyclohexane ring was active on both target proteins, cytotoxic on a micromolar range and was found to induce apoptosis through a classical pathway.

CiteXplore: 25266781

DOI: 10.1016/j.bmcl.2014.09.004