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Wiley, ChemMedChem, 12(4), p. 2060-2069, 2009

DOI: 10.1002/cmdc.200900262

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Investigation of Trypanothione Reductase as a Drug Target in Trypanosoma brucei

Journal article published in 2009 by Daniel Spinks, Emma J. Shanks, Laura A. T. Cleghorn ORCID, Stuart McElroy, Deuan Jones, Daniel James, Alan H. Fairlamb, Julie A. Frearson, Paul G. Wyatt, Ian H. Gilbert
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This paper is available in a repository.

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Abstract

There is an urgent need for new drugs for the treatment of tropical parasitic diseases such as human African trypanosomiasis, which is caused by Trypanosoma brucei. The enzyme trypanothione reductase (TryR) is a potential drug target within these organisms. Herein we report the screening of a 62,000 compound library against T. brucei TryR. Further work was undertaken to optimise potency and selectivity of two novel-compound series arising from the enzymatic and whole parasite screens and mammalian cell counterscreens. Both of these series, containing either a quinoline or pyrimidinopyrazine scaffold, yielded low micromolar inhibitors of the enzyme and growth of the parasite. The challenges of inhibiting TryR with druglike molecules is discussed.