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

14 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.
LanguageEnglish
Pages2001-2006
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number6
DOIs
Publication statusPublished - Mar 2010

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Antiparasitic Agents
Trypanosoma brucei brucei
Enzymes
Drug Discovery
Cytotoxicity
Caspases
Substrate Specificity
Pharmaceutical Preparations
Substrates
In Vitro Techniques

Keywords

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

Cite this

Berg, M., van der Veken, P., Joossens, J., Muthusamy, V., Breugelmans, M., Moss, C. X., ... Coombs, G. H. (2010). Design and evaluation of Trypanosoma brucei metacaspase inhibitors. Bioorganic and Medicinal Chemistry Letters, 20(6), 2001-2006. https://doi.org/10.1016/j.bmcl.2010.01.099
Berg, M. ; van der Veken, P. ; Joossens, J. ; Muthusamy, V. ; Breugelmans, M. ; Moss, C.X. ; Rudolf, J. ; Coombs, G.H. / Design and evaluation of Trypanosoma brucei metacaspase inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 6. pp. 2001-2006.
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Berg, M, van der Veken, P, Joossens, J, Muthusamy, V, Breugelmans, M, Moss, CX, Rudolf, J & Coombs, GH 2010, 'Design and evaluation of Trypanosoma brucei metacaspase inhibitors' Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 6, pp. 2001-2006. https://doi.org/10.1016/j.bmcl.2010.01.099

Design and evaluation of Trypanosoma brucei metacaspase inhibitors. / Berg, M.; van der Veken, P.; Joossens, J.; Muthusamy, V.; Breugelmans, M.; Moss, C.X.; Rudolf, J.; Coombs, G.H.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 6, 03.2010, p. 2001-2006.

Research output: Contribution to journalArticle

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Berg M, van der Veken P, Joossens J, Muthusamy V, Breugelmans M, Moss CX et al. Design and evaluation of Trypanosoma brucei metacaspase inhibitors. Bioorganic and Medicinal Chemistry Letters. 2010 Mar;20(6):2001-2006. https://doi.org/10.1016/j.bmcl.2010.01.099