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Structure-guided development of selective TbcatB inhibitors.

ABSTRACT: The trypanosomal cathepsin TbcatB is essential for parasite survival and is an attractive therapeutic target. Herein we report the structure-guided development of TbcatB inhibitors with specificity relative to rhodesain and human cathepsins B and L. Inhibitors were tested for enzymatic activity, trypanocidal activity, and general cytotoxicity. These data chemically validate TbcatB as a drug target and demonstrate that it is possible to potently and selectively inhibit TbcatB relative to trypanosomal and human homologues.

SUBMITTER: Mallari JP

PROVIDER: S-EPMC2762491 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Structure-guided development of selective TbcatB inhibitors.

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

Journal of medicinal chemistry 20091001 20

The trypanosomal cathepsin TbcatB is essential for parasite survival and is an attractive therapeutic target. Herein we report the structure-guided development of TbcatB inhibitors with specificity relative to rhodesain and human cathepsins B and L. Inhibitors were tested for enzymatic activity, trypanocidal activity, and general cytotoxicity. These data chemically validate TbcatB as a drug target and demonstrate that it is possible to potently and selectively inhibit TbcatB relative to trypanos ...[more]

PMID: 19769357

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