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.
|Title of host publication||Trypanosomatid Diseases: Molecular Routes to Drug Discovery|
|Editors||Timo Jager, Oliver Koch, Leopold Flohe|
|Place of Publication||Weinheim Germany|
|Publisher||Wiley-VCH Verlag GmbH & Co. KGaA|
|Pages||37 - 56|
|Number of pages||20|
|Publication status||Published - 2013|