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ID: ALA2169820

Journal: Eur J Med Chem

Title: Synthesis and biological activities of polyquinoline derivatives: new Bcl-2 family protein modulators.

Authors: Saugues E, Debaud AL, Anizon F, Bonnefoy N, Moreau P.

Abstract: The synthesis of quinoline derivatives, designed to interact with Bcl-x(L), and to inhibit its interaction with pro-apoptotic partners, is described and their biological effects investigated. We showed that 5 out of 28 synthetized compounds restored cell death of 3T3 cells overexpressing Bcl-x(L) following serum starvation. Active compounds were further characterized for their binding capacity to the anti-apoptotic member of the Bcl-2 family, Bcl-x(L) as well as Bcl-2, Bfl-1 and Mcl-1, and for their pro-apoptotic activities toward lymphoid tumor cells and peripheral blood mononuclear cells. Altogether our results indicate that dimeric, rather than trimeric quinoline derivatives, represent a new attractive class of BH3 mimetics for cancer therapy.

CiteXplore: 23047228

DOI: 10.1016/j.ejmech.2012.09.012