Synthesis, cytotoxicity of new 4-arylidene curcumin analogues and their multi-functions in inhibition of both NF-κB and Akt signalling

Eur J Med Chem. 2012 Sep:55:346-57. doi: 10.1016/j.ejmech.2012.07.039. Epub 2012 Jul 31.

Abstract

A series of new 4-arylidene curcumin analogues (4-arylidene-1,7-bisarylhepta-1,6-diene-3,5-diones) were synthesized and found to be potent antiproliferative agents against a panel of cancer cell lines at submicromolar to low micromolar concentrations by SRB assay. Their inhibitory abilities against NF-κB was evaluated by High Content Analysis (HCA) based immunofluorescence assay; and the Akt signalling inhibition was determined by fluorescence polarization assay and western blot respectively. The Structure-Activity Relationship was discussed. Our results revealed that 4-arylidene curcumin analogues may work in a multi-targets manner in cancer cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemistry Techniques, Synthetic
  • Curcumin / chemical synthesis*
  • Curcumin / chemistry
  • Curcumin / metabolism
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Molecular Docking Simulation
  • NF-kappa B / metabolism*
  • Phosphorylation / drug effects
  • Protein Conformation
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Protein Transport
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / chemistry
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents
  • NF-kappa B
  • Protein Kinase Inhibitors
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3
  • Curcumin