Pharmacological metabolomics in trypanosomes

Darren John Creek, Isabel M Vincent, Michael P Barrett

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

1 Citation (Scopus)

Abstract

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.
Original languageEnglish
Title of host publicationTrypanosomatid Diseases: Molecular Routes to Drug Discovery
EditorsTimo Jager, Oliver Koch, Leopold Flohe
Place of PublicationWeinheim Germany
PublisherWiley-VCH Verlag GmbH & Co. KGaA
Pages37 - 56
Number of pages20
ISBN (Print)9783527332557
DOIs
Publication statusPublished - 2013
Externally publishedYes

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