The trypanosome alternative oxidase: a potential drug target?

Stefanie K. Menzies, Lindsay B. Tulloch, Gordon J. Florence, Terry K. Smith

Research output: Contribution to journalReview article

13 Citations (Scopus)
94 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)175-183
Number of pages9
JournalParasitology
Volume145
Issue number2
Early online date29 Nov 2016
DOIs
Publication statusPublished - Feb 2018

Keywords

  • Animals
  • Drug Discovery
  • Humans
  • Mitochondria/drug effects
  • Mitochondrial Proteins/chemistry
  • Oxidoreductases/chemistry
  • Plant Proteins/chemistry
  • Trypanocidal Agents/pharmacology
  • Trypanosoma brucei brucei/drug effects
  • Trypanosomiasis, African/drug therapy

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  • Cite this

    Menzies, S. K., Tulloch, L. B., Florence, G. J., & Smith, T. K. (2018). The trypanosome alternative oxidase: a potential drug target? Parasitology, 145(2), 175-183. https://doi.org/10.1017/S0031182016002109