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

Producción científica: Article › revisión exhaustiva

57 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	2883-2885
Número de páginas	3
Publicación	Bioorganic and Medicinal Chemistry Letters
Volumen	18
N.º	9
DOI	https://doi.org/10.1016/j.bmcl.2008.03.083
Estado	Published - may 1 2008

Nota bibliográfica

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.

Financiación

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.

Financiadores	Número del financiador
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases	P01AI035707
St. Jude Children's Research Hospital
American Lebanese Syrian Associated Charities

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

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

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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. ",

year = "2008",

month = may,

day = "1",

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

language = "English",

volume = "18",

pages = "2883--2885",

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TY - JOUR

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

UR - https://www.scopus.com/pages/publications/42949123155

UR - https://www.scopus.com/pages/publications/42949123155#tab=citedBy

U2 - 10.1016/j.bmcl.2008.03.083

DO - 10.1016/j.bmcl.2008.03.083

M3 - Article

C2 - 18420405

AN - SCOPUS:42949123155

SN - 0960-894X

VL - 18

SP - 2883

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

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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Huella

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