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.
Keywords: Apoptosis, Bcl-xL, B-16-F10 cells, BRET, cancer, melanoma, pyrazoles.
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