Design, synthesis and evaluation of (E)-alpha-benzylthio chalcones as novel inhibitors of BCR-ABL kinase

Bioorg Med Chem. 2010 Mar 15;18(6):2317-2326. doi: 10.1016/j.bmc.2010.01.051. Epub 2010 Jan 25.

Abstract

Novel (E)-alpha-benzylthio chalcones are reported with preliminary in vitro activity data indicating that several of them are potent inhibitors (comparable to imatinib, the reference compound) of BCR-ABL phosphorylation in leukemic K562 cells, known to express high levels of BCR-ABL. The ability of such compounds to significantly inhibit K562 cell proliferation suggests that this scaffold could be a promising lead for the development of anticancer agents that are able to block BCR-ABL phosphorylation in leukemic cells.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Proliferation / drug effects
  • Chalcones / chemical synthesis*
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Fusion Proteins, bcr-abl / antagonists & inhibitors*
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • K562 Cells
  • Molecular Structure
  • Phosphorylation
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • (E)-alpha-benzylthio chalcone
  • Chalcones
  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl