Trypanocidal Activity of β-Lactone-γ-Lactam Proteasome Inhibitors

Dietmar Steverding, Xia Wang, Barbara C. M. Potts, Michael A. Palladino

Research output: Contribution to journalArticle

Abstract

Four beta-lactone-gamma-lactam proteasome inhibitors of natural origin were tested for their trypanocidal activities IN VITRO using culture-adapted bloodstream forms of TRYPANOSOMA BRUCEI. All four compounds displayed activities in the nanomolar range. The most trypanocidal compounds with 50?% growth inhibition (GI (50)) values of around 3 nM were the bromine and iodine analogues of salinosporamide A, a potent proteasome inhibitor produced by the marine actinomycete SALINISPORA TROPICA. In general, trypanosomes were more susceptible to the compounds than were human HL-60 cells. The data support the potential of beta-lactone-gamma-lactam proteasome inhibitors for rational anti-trypanosomal drug development.
Original languageEnglish
Pages (from-to)131-134
Number of pages4
JournalPlanta Medica
Volume78
Issue number2
Early online date27 Oct 2011
DOIs
Publication statusPublished - 2012

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