Pharmacological metabolomics in trypanosomes

Creek, D.J., Vincent, I.M. and Barrett, M.P. (2013) Pharmacological metabolomics in trypanosomes. In: Jäger, T., Koch, O. and Flohé, L. (eds.) Trypanosomatid Diseases. Series: Drug discovery in infectious diseases (4). John Wiley and Sons, Inc.: Weinheim, pp. 37-56. ISBN 9783527670390 (doi:10.1002/9783527670383.ch3)

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Many drugs act by perturbing aspects of cellular metabolism. Human African trypanosomiasis can be treated with five drugs, depending on the causative subspecies and the stage of the disease. For only one drug, eflornithine (difluoromethylornithine), has a mode of action been ascertained – it inhibits ornithine decarboxylase, a key enzyme in polyamine biosynthesis. Modes of action remain unknown for the other drugs, which include the organic arsenical melarsoprol, the naphthalene suramin, the diamidine pentamidine, and the nitrofuran nifurtimox, although it has recently been shown that nifurtimox acts following its metabolism to a reactive trinitrile derivative. Metabolomics aims to quantify all low-molecular-weight chemicals within a given system. Metabolomic techniques have recently been developed and applied to trypanosomes, and might be expected to reveal how drugs perturb metabolism. Here, we review methods to study the trypanosome's metabolome and discuss the current knowledge with respect to the effects of anti-trypanosomal drugs on parasite metabolism.

Item Type:Book Sections
Glasgow Author(s) Enlighten ID:Vincent, Dr Isabel and Creek, Dr Darren and Barrett, Professor Michael
Authors: Creek, D.J., Vincent, I.M., and Barrett, M.P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Publisher:John Wiley and Sons, Inc.

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