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