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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Kelly, John M.³  Taylor, Martin C.³  Horn, David³  Loza, Einars⁴  Kalvinsh, Ivars^1,4  Bjorkling, Fredrik² 

[1] TopoTarget AS, Symb, DK-2100 Copenhagen, Denmark

[2] Univ Copenhagen, Fac Hlth & Med Sci, Dept Mol Drug Res, DK-2100 Copenhagen, Denmark

[3] London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England

[4] Latvian Inst Organ Synth, LV-1006 Riga, Latvia

关键词: Anti-parasitic activity;    Trypanosoma brucei;    Histone deacetylase inhibitors;    Hydroxamic acids;   

DOI  :  10.1016/j.bmcl.2012.01.072

来源: Elsevier

【 摘 要 】

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 IC50 of 34 nM. These results identify lead compounds with potential for the development of a novel class of trypanocidal agent. (c) 2012 Elsevier Ltd. All rights reserved.

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