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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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,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User: Pure Connector
Date Deposited: 24 Jan 2014 12:42
Last Modified: 22 Jul 2024 00:20
DOI: 10.1007/s00436-004-1253-y

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