title: Design, synthesis and biological evaluation of new inhibitors of Bax/Bcl-xL interaction in cancer cells.
abstract: We describe the synthesis of a series of new molecules containing phenol and triazoles moieties, compounds which have been evaluated for their ability to inhibit Bax/Bcl-xL interactions in cancer cells, by using BRET assays, and to induce cell death. Several derivatives exhibit a very promising activity, being more potent than the reference compounds acylpyrogallol A and ABT-737. These preliminary results demonstrate that derivatives of this family can be attractive to develop new molecules with potent anticancer activity.
authors.affiliation: Université de Rennes 1, Institut des Sciences Chimiques de Rennes, CNRS UMR 6226, Avenue du Général Leclerc, 35042 Rennes Cedex, France.
authors.forename: Duc Duy
authors.initials: DD
authors.lastname: Vo
authors.affiliation: UMR 892 INSERM/6299 CNRS/Université de Nantes, Team 8 "Cell survival and tumor escape in breast cancer", Institut de Recherche Thérapeutique de l'Université de Nantes, 8 quai Moncousu, BP 70721, 44007 Nantes Cedex 1, France; Institut de Cancérologie de l'Ouest, Centre de Lutte contre le Cancer René Gauducheau, Boulevard Jacques Monod, 44805 Saint Herblain-Nantes Cedex, France; Plateforme IMPACT®, Biogenouest Institut de Recherche Thérapeutique de l'Université de Nantes, 8 quai Moncousu, BP 70721, 44007 Nantes Cedex 1, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Gautier
authors.affiliation: UMR 892 INSERM/6299 CNRS/Université de Nantes, Team 8 "Cell survival and tumor escape in breast cancer", Institut de Recherche Thérapeutique de l'Université de Nantes, 8 quai Moncousu, BP 70721, 44007 Nantes Cedex 1, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Barillé-Nion
authors.affiliation: UMR 892 INSERM/6299 CNRS/Université de Nantes, Team 8 "Cell survival and tumor escape in breast cancer", Institut de Recherche Thérapeutique de l'Université de Nantes, 8 quai Moncousu, BP 70721, 44007 Nantes Cedex 1, France; Institut de Cancérologie de l'Ouest, Centre de Lutte contre le Cancer René Gauducheau, Boulevard Jacques Monod, 44805 Saint Herblain-Nantes Cedex, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Juin
authors.affiliation: Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint Grégoire, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Levoin
authors.affiliation: Université de Rennes 1, Institut des Sciences Chimiques de Rennes, CNRS UMR 6226, Avenue du Général Leclerc, 35042 Rennes Cedex, France. Electronic address: Rene.Gree@univ-rennes1.fr.
authors.forename: René
authors.initials: R
authors.lastname: Grée
mesh_terms: D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D010636:Phenols; D014230:Triazoles; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
keywords: Apoptosis; BRET; Bax; Bcl-xL; Cancer; Polyphenol; Triazoles