Design and evaluation of Trypanosoma brucei metacaspase inhibitors

M. Berg, P. van der Veken, J. Joossens, V. Muthusamy, M. Breugelmans, C.X. Moss, J. Rudolf, G.H. Coombs

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2001-2006
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number6
DOIs
Publication statusPublished - Mar 2010

Keywords

  • trypanosoma brucei
  • metacaspase
  • inhibitor
  • african trypanosomiasis
  • sleeping sickness
  • protease inhibitor

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