The trypanosome alternative oxidase: a potential drug target?

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

doi:10.1017/S0031182016002109

The trypanosome alternative oxidase: a potential drug target?

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

Drug Discovery Unit

Research output: Contribution to journal › Review article › peer-review

29 Citations (Scopus)

162 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 language	English
Pages (from-to)	175-183
Number of pages	9
Journal	Parasitology
Volume	145
Issue number	2
Early online date	29 Nov 2016
DOIs	https://doi.org/10.1017/S0031182016002109
Publication status	Published - 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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10.1017/S0031182016002109

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Cite this

@article{91a0f3941c7a4de6b914732b7f001244,

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.",

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",

author = "Menzies, {Stefanie K.} and Tulloch, {Lindsay B.} and Florence, {Gordon J.} and Smith, {Terry K.}",

year = "2018",

month = feb,

doi = "10.1017/S0031182016002109",

language = "English",

volume = "145",

pages = "175--183",

journal = "Parasitology",

issn = "0031-1820",

publisher = "Cambridge University Press",

number = "2",

}

TY - JOUR

T1 - The trypanosome alternative oxidase

T2 - a potential drug target?

AU - Menzies, Stefanie K.

AU - Tulloch, Lindsay B.

AU - Florence, Gordon J.

AU - Smith, Terry K.

PY - 2018/2

Y1 - 2018/2

N2 - 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.

AB - 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.

KW - Animals

KW - Drug Discovery

KW - Humans

KW - Mitochondria/drug effects

KW - Mitochondrial Proteins/chemistry

KW - Oxidoreductases/chemistry

KW - Plant Proteins/chemistry

KW - Trypanocidal Agents/pharmacology

KW - Trypanosoma brucei brucei/drug effects

KW - Trypanosomiasis, African/drug therapy

U2 - 10.1017/S0031182016002109

DO - 10.1017/S0031182016002109

M3 - Review article

C2 - 27894362

SN - 0031-1820

VL - 145

SP - 175

EP - 183

JO - Parasitology

JF - Parasitology

IS - 2

ER -

The trypanosome alternative oxidase: a potential drug target?

Abstract

Keywords

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