Trypanocidal activities of trileucine methyl vinyl sulfone proteasome inhibitors

Steverding, Dietmar, Spackman, Robert W, Royle, Howard J and Glenn, Robert J (2005) Trypanocidal activities of trileucine methyl vinyl sulfone proteasome inhibitors. Parasitology Research, 95 (1). pp. 73-76. ISSN 0932-0113

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Abstract

Previous studies have shown that proteasome inhibitors are novel agents for chemotherapy of human African trypanosomiasis or sleeping sickness. In this study, five peptide trileucine methyl vinyl sulfones with different N-terminal substituents were tested for their trypanocidal activities in vitro using culture-adapted bloodstream forms of Trypanosoma brucei. Two inhibitors displayed promising anti-trypanosomal activities with ED50 values in the sub-micromolar range. Higher trypanocidal activity of the compounds generally corresponded to a higher k(obs)/[I] value for inhibition of the trypsin-like activity but not for the inhibition of the chymotrypsin-like activity of the proteasome. These data suggest that inhibitors with strong activity against the trypsin-like activity of the proteasome are the rational choice for future anti-sleeping sickness drug development.

Item Type: Article
Uncontrolled Keywords: animals,drug evaluation, preclinical,oligopeptides,peptide hydrolases,proteasome endopeptidase complex,proteasome inhibitors,sulfones,trypanocidal agents,trypanosoma brucei brucei,trypsin inhibitors
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 24 Jan 2014 12:42
Last Modified: 21 Apr 2020 22:39
URI: https://ueaeprints.uea.ac.uk/id/eprint/46777
DOI: 10.1007/s00436-004-1253-y

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