Details

Autor(en) / Beteiligte

• Abou Samra, Alma
• Robert, Aude
• Gov, Crystal
• Favre, Loëtitia
• Eloy, Laure
• Jacquet, Eric
• Bignon, Jérôme
• Wiels, Joëlle
• Desrat, Sandy
• Roussi, Fanny

Titel

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

Ist Teil von

• European journal of medicinal chemistry, 2018-03, Vol.148, p.26-38

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. [Display omitted]