Design, synthesis and biological evaluation of new inhibitors of Bax/Bcl-xL interaction in cancer cells

Bioorg Med Chem Lett. 2014 Apr 1;24(7):1758-61. doi: 10.1016/j.bmcl.2014.02.035. Epub 2014 Feb 24.

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.

Keywords: Apoptosis; BRET; Bax; Bcl-xL; Cancer; Polyphenol; Triazoles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • HeLa Cells
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Phenols / chemical synthesis
  • Phenols / chemistry
  • Phenols / pharmacology*
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology*
  • bcl-2-Associated X Protein / antagonists & inhibitors*
  • bcl-2-Associated X Protein / metabolism
  • bcl-X Protein / antagonists & inhibitors*
  • bcl-X Protein / metabolism

Substances

  • Phenols
  • Triazoles
  • bcl-2-Associated X Protein
  • bcl-X Protein