title: Preliminary Studies on the Activity of Mixed Polyphenol-Heterocyclic Systems Against B16-F10 Melanoma Cancer Cells.
abstract: The Bcl-2 family includes 26 proteins involved in apoptosis. Cancer cells can develop the ability to avoid apoptosis through the upregulation and/or down regulation of such proteins Bax, Bcl-xL or Mcl-1, especially during chemoresistance progress. These proteins engaged in a network of dynamic interactions that control apoptosis triggering have become attractive therapeutic targets in cancers including melanoma. Among them, the Bax/Bcl-xL interaction appears critical in maintaining mitochondria integrity. Therefore a series of mixed polyphenol-heterocyclic molecules, were rationally designed by molecular docking as Bax/Bcl-xL inhibitors. It has been screened against B16-F10 melanoma cancer cells for a preliminary investigation of their cytotoxicity. All these compounds exhibited a significant cytotoxicity against these cancer cells, in the 0.3-6 .M range. A pyrazole-type molecule, which had a submicromolar IC50 value with an excellent selectivity index (14), is the most promising derivative for further development.
authors.forename: Duc
authors.initials: D
authors.lastname: Duy Vo
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rouaud
authors.forename: Francoise
authors.initials: F
authors.lastname: Le Devehat
authors.forename: Fabien
authors.initials: F
authors.lastname: Gautier
authors.forename: Sophie
authors.initials: S
authors.lastname: Barillé-Nion
authors.forename: Philippe
authors.initials: P
authors.lastname: Juin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Levoin
authors.forename: Joël
authors.initials: J
authors.lastname: Boustie
authors.affiliation: Université de Rennes 1, Institut des Sciences Chimiques de Rennes, CNRS UMR 6226, Avenue du Général Leclerc, 35042 Rennes Cedex, France. rene.gree@univ-rennes1.fr.
authors.forename: René
authors.initials: R
authors.lastname: Grée
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D060807:Bioluminescence Resonance Energy Transfer Techniques; D002396:Catechols / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D008546:Melanoma, Experimental; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors; D051020:bcl-X Protein / Q000037:antagonists & inhibitors
chemical_list: C000621019:3-(4-fluorobenzyl)-5-(3-(4-phenoxyphenyl)-1H-pyrazol- 5-yl)benzene-1,2-diol; D000970:Antineoplastic Agents; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D002396:Catechols; D011720:Pyrazoles; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein