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: Stefanie K Menzies, Lindsay B Tulloch, Gordon J Florence, Terry K Smith
• Journal: Parasitology (Parasitology) Vol. 145 Issue 2 Pg. 175-183 (02 2018) ISSN: 1469-8161 [Electronic] England
• PMID: 27894362 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Mitochondrial Proteins
• Plant Proteins
• Trypanocidal Agents
• Oxidoreductases
• alternative oxidase

Topics

• Animals
• Drug Discovery
• Humans
• Mitochondria (drug effects)
• Mitochondrial Proteins (chemistry, drug effects, metabolism)
• Oxidoreductases (chemistry, drug effects, metabolism)
• Plant Proteins (chemistry, drug effects, metabolism)
• Trypanocidal Agents (pharmacology)
• Trypanosoma brucei brucei (drug effects, enzymology, metabolism)
• Trypanosomiasis, African (drug therapy, parasitology)