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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.

SUBMITTER: Mallari JP

PROVIDER: S-EPMC2435229 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB.

Mallari Jeremy P JP Shelat Anang A Kosinski Aaron A Caffrey Conor R CR Connelly Michele M Zhu Fangyi F McKerrow James H JH Guy R Kiplin RK

Bioorganic & medicinal chemistry letters 20080408 9

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. bruce ...[more]

PMID: 18420405

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