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DOI: 10.1055/s-0031-1280315
© Georg Thieme Verlag KG Stuttgart · New York
Trypanocidal Activity of β-Lactone-γ-Lactam Proteasome Inhibitors
Publication History
received August 4, 2011
revised September 29, 2011
accepted October 6, 2011
Publication Date:
27 October 2011 (online)

Abstract
Four β-lactone-γ-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 (GI50) 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 β-lactone-γ-lactam proteasome inhibitors for rational anti-trypanosomal drug development.
Key words
Trypanosoma brucei - sleeping sickness - β-lactone-γ-lactam proteasome inhibitors - trypanocidals
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Dietmar Steverding
BioMedical Research Centre
Norwich Medical School
University of East Anglia
Norwich Research Park
Norwich NR4 7TJ
United Kingdom
Phone: +44 16 03 59 12 91
Fax: +44 16 03 59 17 50
Email: dsteverding@hotmail.com