Potent histone deacetylase inhibitors: N-hydroxybenzamides with antitumor activities

Bioorg Med Chem. 2004 Aug 15;12(16):4351-60. doi: 10.1016/j.bmc.2004.06.020.

Abstract

The screening tests of N-hydroxybenzamides for their HDAC-inhibitory activities led to the discovery of the promising compounds with a 2-naphthylcarbonyl group and with a 1,4-biphenylcarbonyl group. These compounds were further modified to optimize their physico-chemical profile. As a result, the inhibitor with a 6-amino-2-naphthylcarbonyl was obtained, which showed not only promising growth inhibitions against a panel of tumor cells, but also an improved water solubility. It exhibited the maximal 185% of survival rate (%T/C) in a in vivo experiment with P388 cell-inoculated mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Benzamides / chemical synthesis*
  • Benzamides / pharmacology*
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Female
  • Histone Deacetylase Inhibitors*
  • Humans
  • Mice
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Benzamides
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors