Synthesis and biological evaluation of N-aryl salicylamides with a hydroxamic acid moiety at 5-position as novel HDAC-EGFR dual inhibitors

Bioorg Med Chem. 2012 Jul 15;20(14):4405-12. doi: 10.1016/j.bmc.2012.05.034. Epub 2012 May 29.

Abstract

A novel series of N-aryl salicylamides with a hydroxamic acid moiety at 5-position were synthesized efficiently. Their activities against EGFR kinase and HDACs were evaluated. All compounds displayed inhibitory activity against EGFR and HDACs. The antiproliferative activities of synthesized compounds were evaluated by MTT method against human cancer cell lines A431, A549 and HL-60. Compound 1o showed the most potent inhibitory activity against A431 and A549. Compounds 1k and 1n exhibited higher potency against HL-60 than gefitinib and SAHA. N-Aryl salicylamides with a hydroxamic acid moiety at 5-position is another new HDAC-EGFR dual inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • HL-60 Cells
  • Histone Deacetylase Inhibitors / chemical synthesis*
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / toxicity
  • Histone Deacetylases / chemistry*
  • Histone Deacetylases / metabolism
  • Humans
  • Hydroxamic Acids / chemistry*
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / toxicity
  • Salicylamides / chemical synthesis
  • Salicylamides / chemistry*
  • Salicylamides / toxicity
  • Structure-Activity Relationship

Substances

  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Protein Kinase Inhibitors
  • Salicylamides
  • ErbB Receptors
  • Histone Deacetylases