title: The trypanosome alternative oxidase: a potential drug target?
abstract: New drugs against Trypanosoma brucei, the causative agent of Human African Trypanosomiasis, are urgently needed to replace the highly toxic and largely ineffective therapies currently used. The trypanosome alternative oxidase (TAO) is an essential and unique mitochondrial protein in these parasites and is absent from mammalian mitochondria, making it an attractive drug target. The structure and function of the protein are now well characterized, with several inhibitors reported in the literature, which show potential as clinical drug candidates. In this review, we provide an update on the functional activity and structural aspects of TAO. We then discuss TAO inhibitors reported to date, problems encountered with in vivo testing of these compounds, and discuss the future of TAO as a therapeutic target.
authors.affiliation: Biomedical Sciences Research Complex, University of St Andrews,St Andrews, Fife, Scotland KY16 9ST,UK.
authors.forename: Stefanie K
authors.identifier: 0000-0002-9273-9296
authors.initials: SK
authors.lastname: Menzies
authors.affiliation: Biomedical Sciences Research Complex, University of St Andrews,St Andrews, Fife, Scotland KY16 9ST,UK.
authors.forename: Lindsay B
authors.initials: LB
authors.lastname: Tulloch
authors.affiliation: Biomedical Sciences Research Complex, University of St Andrews,St Andrews, Fife, Scotland KY16 9ST,UK.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Florence
authors.affiliation: Biomedical Sciences Research Complex, University of St Andrews,St Andrews, Fife, Scotland KY16 9ST,UK.
authors.forename: Terry K
authors.initials: TK
authors.lastname: Smith
mesh_terms: D000818:Animals; D055808:Drug Discovery; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D010940:Plant Proteins / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D014344:Trypanocidal Agents / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000469:parasitology; D000099188:Alternative Oxidase
chemical_list: D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D010940:Plant Proteins; D014344:Trypanocidal Agents; D000099188:Alternative Oxidase
keywords: 
                 Trypanosoma brucei
              ; Trypanosome alternative oxidase; chemotherapy; drug discovery; human African trypanosomiasis; sleeping sickness