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^*

^*Corresponding author for this work

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

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
Event	British-Society-for-Parasitology (BSP) Autumn Symposium on Microbial Protein Targets - Towards Understanding and Intervention - Durham Duration: 14 Sept 2016 → 16 Sept 2016

Keywords

Trypanosoma alternative oxidase
Drug discovery
Chemotherapy
Human African trypanosomiasis
Sleeping sickness
Trypanosoma brucei

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1017/S0031182016002109

Smith_2016_Parasitology_Trypanosome_AAM
© Cambridge University Press 2016. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at www.cambridge.org / https://doi.org/10.1017/S0031182016002109
Accepted author manuscript, 1.02 MB

Natural Product Drug Discovery: Natural Product Drug Discovery: Design and Development of Novel Tryoanosoma brucei Inhibitors
Florence, G. J. (PI)
The Leverhulme Trust
1/03/13 → 30/11/18
Project: Standard

Cite this

@article{d385edaab1ae40bb8351893c8752e709,

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 = "Trypanosoma alternative oxidase, Drug discovery, Chemotherapy, Human African trypanosomiasis, Sleeping sickness, Trypanosoma brucei ",

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",

note = "British-Society-for-Parasitology (BSP) Autumn Symposium on Microbial Protein Targets - Towards Understanding and Intervention ; Conference date: 14-09-2016 Through 16-09-2016",

}

TY - JOUR

T1 - The trypanosome alternative oxidase

T2 - British-Society-for-Parasitology (BSP) Autumn Symposium on Microbial Protein Targets - Towards Understanding and Intervention

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 - Trypanosoma alternative oxidase

KW - Drug discovery

KW - Chemotherapy

KW - Human African trypanosomiasis

KW - Sleeping sickness

KW - Trypanosoma brucei

U2 - 10.1017/S0031182016002109

DO - 10.1017/S0031182016002109

M3 - Review article

SN - 0031-1820

VL - 145

SP - 175

EP - 183

JO - Parasitology

JF - Parasitology

IS - 2

Y2 - 14 September 2016 through 16 September 2016

ER -

The trypanosome alternative oxidase: a potential drug target?

Abstract

Keywords

UN SDGs

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Projects

Natural Product Drug Discovery: Natural Product Drug Discovery: Design and Development of Novel Tryoanosoma brucei Inhibitors

Cite this