Parasitology Research 2005-01-01

Trypanocidal activities of trileucine methyl vinyl sulfone proteasome inhibitors.

Dietmar Steverding, Robert W Spackman, Howard J Royle, Robert J Glenn

文献索引：Parasitol. Res. 95(1) , 73-6, (2005)

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摘要

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.