title: Determination of antiprotozoal drug mechanisms by metabolomics approaches.
abstract: The discovery, development and optimal utilization of pharmaceuticals can be greatly enhanced by knowledge of their modes of action. However, many drugs currently on the market act by unknown mechanisms. Untargeted metabolomics offers the potential to discover modes of action for drugs that perturb cellular metabolism. Development of high resolution LC-MS methods and improved data analysis software now allows rapid detection of drug-induced changes to cellular metabolism in an untargeted manner. Several studies have demonstrated the ability of untargeted metabolomics to provide unbiased target discovery for antimicrobial drugs, in particular for antiprotozoal agents. Furthermore, the utilization of targeted metabolomics techniques has enabled validation of existing hypotheses regarding antiprotozoal drug mechanisms. Metabolomics approaches are likely to assist with optimization of new drug candidates by identification of drug targets, and by allowing detailed characterization of modes of action and resistance of existing and novel antiprotozoal drugs.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, 30 Flemington Rd, Parkville, Victoria 3010, Australia.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Creek
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, and Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Barrett
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D002853:Chromatography, Liquid; D057225:Data Mining; D004351:Drug Resistance; D006801:Humans; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D055432:Metabolomics; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism*; D012984:Software; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000981:Antiprotozoal Agents