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Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Preliminary Studies on the Activity of Mixed Polyphenol-Heterocyclic Systems Against B16-F10 Melanoma Cancer Cells

Author(s): Duc Duy Vo, Isabelle Rouaud, Francoise Le Devehat, Fabien Gautier, Sophie Barillé-Nion, Philippe Juin, Nicolas Levoin, Joël Boustie and René Grée

Volume 12, Issue 5, 2016

Page: [419 - 425] Pages: 7

DOI: 10.2174/1573406412666160129104603

Price: $65

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.

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


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