1. Preliminary Studies on the Activity of Mixed Polyphenol-Heterocyclic Systems Against B16-F10 Melanoma Cancer Cells.
- Author
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Duy Vo D, Rouaud I, Le Devehat F, Gautier F, Barillé-Nion S, Juin P, Levoin N, Boustie J, and Grée R
- Subjects
- Antineoplastic Agents chemical synthesis, Apoptosis drug effects, Bioluminescence Resonance Energy Transfer Techniques, Catechols chemical synthesis, Cell Line, Tumor, HeLa Cells, Humans, Melanoma, Experimental, Molecular Docking Simulation, Pyrazoles chemical synthesis, bcl-2-Associated X Protein antagonists & inhibitors, bcl-X Protein antagonists & inhibitors, Antineoplastic Agents pharmacology, Catechols pharmacology, Pyrazoles pharmacology
- 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.
- Published
- 2016
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