Inhibitors of human histone deacetylase with potent activity against the African trypanosome Trypanosoma brucei.
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.
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
John M
JM
Kelly
Martin C
MC
Taylor
David
D
Horn
Einars
E
Loza
Ivars
I
Kalvinsh
Fredrik
F
Björkling
D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000254:growth & development; D014353:Trypanosomiasis, African / Q000188:drug therapy
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D014344:Trypanocidal Agents; D006655:Histone Deacetylases