Design and evaluation of Trypanosoma brucei metacaspase inhibitors

Berg, M. et al. (2010) Design and evaluation of Trypanosoma brucei metacaspase inhibitors. Bioorganic and Medicinal Chemistry Letters, 20(6), pp. 2001-2006. (doi:10.1016/j.bmcl.2010.01.099)

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Publisher's URL: http://dx.doi.org/10.1016/j.bmcl.2010.01.099

Abstract

Metacaspase (MCA) is an important enzyme in <i>Trypanosoma brucei</i>, 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rudolf, Dr Jana and Moss, Dr Catherine and Mottram, Professor Jeremy and Coombs, Professor Graham
Authors: Berg, M., Van der Veken, P., Joossens, J., Muthusamy, V., Breugelmans, M., Moss, C. X., Rudolf, J., Cos, P., Coombs, G. H., Maes, L., Haemers, A., Mottram, J. C., and Augustyns, K.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Bioorganic and Medicinal Chemistry Letters
ISSN:0960-894X
ISSN (Online):1464-3405
Published Online:25 January 2010
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