Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB

Jeremy P. Mallari; Anang Shelat; Aaron Kosinski; Conor R. Caffrey; Michele Connelly; Fangyi Zhu; James H. McKerrow; R. Kiplin Guy

doi:10.1016/j.bmcl.2008.03.083

Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB

Jeremy P. Mallari, Anang Shelat, Aaron Kosinski, Conor R. Caffrey, Michele Connelly, Fangyi Zhu, James H. McKerrow, R. Kiplin Guy

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

55 Scopus citations

Abstract

Human African trypanosomiasis (HAT) is caused by the protozoan parasite Trypanosoma brucei. The cysteine proteases of T. brucei have been shown to be crucial for parasite replication and represent an attractive point for therapeutic intervention. Herein we describe the synthesis of a series of thiosemicarbazones and their activity against the trypanosomal cathepsins TbcatB and rhodesain, as well as human cathepsins L and B. The activity of these compounds was determined against cultured T. brucei, and specificity was assessed with a panel of four mammalian cell lines.

Original language	English
Pages (from-to)	2883-2885
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	9
DOIs	https://doi.org/10.1016/j.bmcl.2008.03.083
State	Published - May 1 2008

Bibliographical note

Funding Information:
This work was supported by the American Lebanese Syrian Associated Charities (ALSAC) and St. Jude Children’s Research Hospital, NIH Grant AI35707, and the Sandler Family Supporting Foundation.

Keywords

African trypanosomiasis
Cathepsins
HAT
Protease inhibitors
Rhodesain
Sleeping sickness
TbCatB
Thiosemicarbazone

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

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

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10.1016/j.bmcl.2008.03.083

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@article{aabfc4622837493ba529ff41e9299785,

title = "Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB",

abstract = "Human African trypanosomiasis (HAT) is caused by the protozoan parasite Trypanosoma brucei. The cysteine proteases of T. brucei have been shown to be crucial for parasite replication and represent an attractive point for therapeutic intervention. Herein we describe the synthesis of a series of thiosemicarbazones and their activity against the trypanosomal cathepsins TbcatB and rhodesain, as well as human cathepsins L and B. The activity of these compounds was determined against cultured T. brucei, and specificity was assessed with a panel of four mammalian cell lines.",

keywords = "African trypanosomiasis, Cathepsins, HAT, Protease inhibitors, Rhodesain, Sleeping sickness, TbCatB, Thiosemicarbazone",

author = "Mallari, {Jeremy P.} and Anang Shelat and Aaron Kosinski and Caffrey, {Conor R.} and Michele Connelly and Fangyi Zhu and McKerrow, {James H.} and Guy, {R. Kiplin}",

note = "Funding Information: This work was supported by the American Lebanese Syrian Associated Charities (ALSAC) and St. Jude Children{\textquoteright}s Research Hospital, NIH Grant AI35707, and the Sandler Family Supporting Foundation. ",

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doi = "10.1016/j.bmcl.2008.03.083",

language = "English",

volume = "18",

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T1 - Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB

AU - Mallari, Jeremy P.

AU - Shelat, Anang

AU - Kosinski, Aaron

AU - Caffrey, Conor R.

AU - Connelly, Michele

AU - Zhu, Fangyi

AU - McKerrow, James H.

AU - Guy, R. Kiplin

N1 - Funding Information: This work was supported by the American Lebanese Syrian Associated Charities (ALSAC) and St. Jude Children’s Research Hospital, NIH Grant AI35707, and the Sandler Family Supporting Foundation.

PY - 2008/5/1

Y1 - 2008/5/1

N2 - Human African trypanosomiasis (HAT) is caused by the protozoan parasite Trypanosoma brucei. The cysteine proteases of T. brucei have been shown to be crucial for parasite replication and represent an attractive point for therapeutic intervention. Herein we describe the synthesis of a series of thiosemicarbazones and their activity against the trypanosomal cathepsins TbcatB and rhodesain, as well as human cathepsins L and B. The activity of these compounds was determined against cultured T. brucei, and specificity was assessed with a panel of four mammalian cell lines.

AB - Human African trypanosomiasis (HAT) is caused by the protozoan parasite Trypanosoma brucei. The cysteine proteases of T. brucei have been shown to be crucial for parasite replication and represent an attractive point for therapeutic intervention. Herein we describe the synthesis of a series of thiosemicarbazones and their activity against the trypanosomal cathepsins TbcatB and rhodesain, as well as human cathepsins L and B. The activity of these compounds was determined against cultured T. brucei, and specificity was assessed with a panel of four mammalian cell lines.

KW - African trypanosomiasis

KW - Cathepsins

KW - HAT

KW - Protease inhibitors

KW - Rhodesain

KW - Sleeping sickness

KW - TbCatB

KW - Thiosemicarbazone

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AN - SCOPUS:42949123155

SN - 0960-894X

VL - 18

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EP - 2885

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 9

ER -

Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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