α-Ketoheterocycles as inhibitors of Leishmania mexicana cysteine protease CPB

Steert, K. et al. (2010) α-Ketoheterocycles as inhibitors of Leishmania mexicana cysteine protease CPB. ChemMedChem, 5(10), pp. 1734-1748. (doi: 10.1002/cmdc.201000265)

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Publisher's URL: http://dx.doi.org/10.1002/cmdc.201000265

Abstract

Cysteine proteases of the papain superfamily are present in nearly all eukaryotes and also play pivotal roles in the biology of parasites. Inhibition of cysteine proteases is emerging as an important strategy to combat parasitic diseases such as sleeping sickness, Chagas disease, and leishmaniasis. Inspired by the in vivo antiparasitic activity of the vinylsulfone-based cysteine protease inhibitors, a series of a-ketoheterocycles were developed as reversible inhibitors of a recombinant L. mexicana cysteine protease, CPB2.8. Three isoxazoles and especially one oxadiazole compound are potent reversible inhibitors of CPB2.8; however, in vitro whole-organism screening against a panel of protozoan parasites did not fully correlate with the observed inhibition of the cysteine protease.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Coombs, Professor Graham and Westrop, Mr Gareth and Mottram, Professor Jeremy
Authors: Steert, K., Berg, M., Mottram, J. C., Westrop, G. D., Coombs, G. H., Cos, P., Maes, L., Joossens, J., Van der Veken, P., Haemers, A., and Augustyns, K.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:ChemMedChem
Publisher:Wiley-VCH Verlag
ISSN:1860-7179
ISSN (Online):1860-7187
Published Online:26 August 2010
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
454141Analysing the roles of petidases in Leishmania infectivity and pathogenicityJeremy MottramMedical Research Council (MRC)G0700127Infection Immunity and Inflammation Life Sciences