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

John M. Kelly; Martin C. Taylor; David Horn; Einars Loza; Ivars Kalvinsh; Fredrik Bjorkling

doi:10.1016/j.bmcl.2012.01.072

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

John M. Kelly, Martin C. Taylor, David Horn, Einars Loza, Ivars Kalvinsh, Fredrik Bjorkling

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	1886-1890
Number of pages	5
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	22
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2012.01.072
Publication status	Published - 1 Mar 2012

Keywords

SLEEPING SICKNESS
Histone deacetylase inhibitors
MARK
SELECTIVITY
Hydroxamic acids
Anti-parasitic activity
CYCLE
ANTIMALARIAL
Trypanosoma brucei

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2012.01.072

Cite this

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title = "Inhibitors of human histone deacetylase with potent activity against the African trypanosome Trypanosoma brucei",

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 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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author = "Kelly, {John M.} and Taylor, {Martin C.} and David Horn and Einars Loza and Ivars Kalvinsh and Fredrik Bjorkling",

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doi = "10.1016/j.bmcl.2012.01.072",

language = "English",

volume = "22",

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journal = "Bioorganic & Medicinal Chemistry Letters",

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T1 - Inhibitors of human histone deacetylase with potent activity against the African trypanosome Trypanosoma brucei

AU - Kelly, John M.

AU - Taylor, Martin C.

AU - Horn, David

AU - Loza, Einars

AU - Kalvinsh, Ivars

AU - Bjorkling, Fredrik

PY - 2012/3/1

Y1 - 2012/3/1

N2 - 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.

AB - 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.

KW - SLEEPING SICKNESS

KW - Histone deacetylase inhibitors

KW - MARK

KW - SELECTIVITY

KW - Hydroxamic acids

KW - Anti-parasitic activity

KW - CYCLE

KW - ANTIMALARIAL

KW - Trypanosoma brucei

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DO - 10.1016/j.bmcl.2012.01.072

M3 - Article

SN - 0960-894X

VL - 22

SP - 1886

EP - 1890

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 5

ER -

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

Abstract

Keywords

UN SDGs

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