Planta Med 2012; 78(2): 131-134
DOI: 10.1055/s-0031-1280315
Biological and Pharmacological Activity
Letters
© Georg Thieme Verlag KG Stuttgart · New York

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

Dietmar Steverding1 , Xia Wang1 , Barbara C. M. Potts2 , Michael A. Palladino2
  • 1BioMedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, UK
  • 2Nereus Pharmaceuticals, Inc., San Diego, California, USA
Further Information

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.

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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