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ID: ALA1155398

Journal: Bioorg Med Chem Lett

Title: Design and evaluation of Trypanosoma brucei metacaspase inhibitors.

Authors: Berg M, Van der Veken P, Joossens J, Muthusamy V, Breugelmans M, Moss CX, Rudolf J, Cos P, Coombs GH, Maes L, Haemers A, Mottram JC, Augustyns K.

Abstract: Metacaspase (MCA) is an important enzyme in Trypanosoma brucei, absent from humans and differing significantly from the orthologous human caspases. Therefore MCA constitutes a new attractive drug target for antiparasitic chemotherapeutics, which needs further characterization to support the discovery of innovative drug candidates. A first series of inhibitors has been prepared on the basis of known substrate specificity and the predicted catalytic mechanism of the enzyme. In this Letter we present the first inhibitors of TbMCA2 with low micromolar enzymatic and antiparasitic activity in vitro combined with low cytotoxicity.

CiteXplore: 20167486

DOI: 10.1016/j.bmcl.2010.01.099