Inhibitors of human histone deacetylase with potent activity against the African trypanosome Trypanosoma brucei

Bioorg Med Chem Lett. 2012 Mar 1;22(5):1886-90. doi: 10.1016/j.bmcl.2012.01.072. Epub 2012 Jan 28.

Abstract

A number of hydroxamic acid derivatives which inhibit human histone deacetylases were investigated for efficacy against cultured bloodstream form Trypanosoma brucei. Three out of the four classes tested displayed significant activity. The majority of compounds blocked parasite growth in the submicromolar range. The most potent was a member of the sulphonepiperazine series with an IC(50) of 34nM. These results identify lead compounds with potential for the development of a novel class of trypanocidal agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HeLa Cells
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism
  • Humans
  • Hydroxamic Acids / chemistry*
  • Hydroxamic Acids / pharmacology*
  • Models, Molecular
  • Trypanocidal Agents / chemistry*
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma brucei brucei / drug effects*
  • Trypanosoma brucei brucei / growth & development
  • Trypanosomiasis, African / drug therapy

Substances

  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Trypanocidal Agents
  • Histone Deacetylases