High-throughput screening affords novel and selective trypanothione reductase inhibitors with anti-trypanosomal activity

descriptionPublicationkeyboard_double_arrow_right Article 01 Mar 2007 United Kingdom English Publisher:Elsevier BVJournal:Bioorganic & Medicinal Chemistry Letters, volume 17, pages 1,280-1,283 (issn: 0960-894X,

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Authors: Martyn, Derek C.; Jones, Deuan C.; Fairlamb, Alan H.; Clardy, Jon;

doi: 10.1016/j.bmcl.2006.12.016

pmid: 17197182

pmc: PMC3428910

High-throughput screening affords novel and selective trypanothione reductase inhibitors with anti-trypanosomal activity

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Abstract

Trypanothione reductase (TR), an enzyme that buffers oxidative stress in trypanosomatid parasites, was screened against commercial libraries containing approximately 134,500 compounds. After secondary screening, four chemotypes were identified as screening positives with selectivity for TR over human glutathione reductase. Thirteen compounds from these four chemotypes were purchased, and their in vitro activity against TR and Trypanosoma brucei is described.

Country

United Kingdom

Related Organizations

University of Dundee
United Kingdom
Harvard University
United States

Keywords

/dk/atira/pure/subjectarea/asjc/1300/1313, 570, Trypanosoma, /dk/atira/pure/subjectarea/asjc/1300/1312, Trypanosoma brucei brucei, Drug Evaluation, Preclinical, name=Clinical Biochemistry, Structure-Activity Relationship, Trypanosomiasis, name=Molecular Medicine, Animals, Humans, NADH, NADPH Oxidoreductases, Enzyme Inhibitors, name=Pharmaceutical Science, /dk/atira/pure/subjectarea/asjc/1300/1303, /dk/atira/pure/subjectarea/asjc/1600/1605, High-throughput screening, name=Biochemistry, name=Molecular Biology, Trypanocidal Agents, Glutathione Reductase, name=Organic Chemistry, /dk/atira/pure/subjectarea/asjc/3000/3002, /dk/atira/pure/subjectarea/asjc/1300/1308, Trypanothione reductase, /dk/atira/pure/subjectarea/asjc/3000/3003, name=Drug Discovery

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