Design, synthesis and molecular docking of α,β-unsaturated cyclohexanone analogous of curcumin as potent EGFR inhibitors with antiproliferative activity

Bioorg Med Chem. 2013 Jan 15;21(2):388-94. doi: 10.1016/j.bmc.2012.11.031. Epub 2012 Dec 2.

Abstract

A type of novel α,β-unsaturated cyclohexanone analogous, which designed based on the curcumin core structure, have been discovered as potential EGFR inhibitors. These compounds exhibit potent antiproliferative activity in two human tumor cell lines (Hep G2 and B16-F10). Among them, compounds I(3) and I(12) displayed the most potent EGFR inhibitory activity (IC(50) = 0.43 μM and 1.54 μM, respectively). Molecular docking of I(12) into EGFR TK active site was also performed. This inhibitor nicely fitting the active site might well explain its excellent inhibitory activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Binding Sites
  • Catalytic Domain
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Curcumin / analogs & derivatives*
  • Curcumin / chemical synthesis
  • Curcumin / toxicity
  • Cyclohexanones / chemistry*
  • Drug Design*
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Hep G2 Cells
  • Humans
  • Molecular Docking Simulation
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / toxicity
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Cyclohexanones
  • Protein Kinase Inhibitors
  • cyclohexanone
  • ErbB Receptors
  • Curcumin