Design and evaluation of Trypanosoma brucei metacaspase inhibitors

作者：Berg Maya; Van der Veken Pieter; Joossens Jurgen; Muthusamy Venkatraj; Breugelmans Matthias; Moss Catherine X; Rudolf Jana; Cos Paul; Coombs Graham H; Maes Louis; Haemers Achiel; Mottram Jeremy C; Augustyns Koen^*

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(6): 2001-2006.

DOI：10.1016/j.bmcl.2010.01.099

• Trypanosoma brucei
• Metacaspase
• Inhibitor
• African trypanosomiasis
• Sleeping sickness
• Protease inhibitor

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.

• 出版日期2010-3-15