Dual inhibitors of the pro-survival proteins Bcl-2 and Mcl-1 derived from natural compound meiogynin A - Archive ouverte HAL
Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2018

Dual inhibitors of the pro-survival proteins Bcl-2 and Mcl-1 derived from natural compound meiogynin A

Résumé

Thirty analogues of natural meiogynin A, a pan-Bcl-2 inhibitor, were prepared in order to elaborate cytotoxic compounds on specific cancer cells overexpressing one or more proteins of the Bcl-2 family. The interaction of all the new analogues with Bcl-xL, Mcl-1 and Bcl-2 proteins was first evaluated by fluorescence polarization assay (FPA) and showed that modulation of the lateral chain has a dramatic impact as subtle changes significantly modify the activity on the target proteins. The acetoxymethyl prodrugs of the two most active compounds were then elaborated to determine their cytotoxicity on B cell lines. A strong cytotoxic effect on BL2, RS4;11 and H929 cells was observed with a triazole prodrug that induces apoptosis.
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Dates et versions

hal-02343193 , version 1 (02-11-2019)

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Citer

Alma Abou Samra, Aude Robert, Crystal Gov, Loëtitia Favre, Laure Eloy, et al.. Dual inhibitors of the pro-survival proteins Bcl-2 and Mcl-1 derived from natural compound meiogynin A. European Journal of Medicinal Chemistry, 2018, 148, pp.26-38. ⟨10.1016/j.ejmech.2018.01.100⟩. ⟨hal-02343193⟩
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