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Design, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors

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Design, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors. / Spinks, Daniel; Torrie, Leah S.; Thompson, Stephen; Harrison, Justin R.; Frearson, Julie A.; Read, Kevin D.; Fairlamb, Alan H.; Wyatt, Paul G.; Gilbert, Ian H.

In: ChemMedChem, Vol. 7, No. 1, 02.01.2012, p. 95-106.

Research output: Contribution to journalArticle

Harvard

Spinks, D, Torrie, LS, Thompson, S, Harrison, JR, Frearson, JA, Read, KD, Fairlamb, AH, Wyatt, PG & Gilbert, IH 2012, 'Design, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors' ChemMedChem, vol 7, no. 1, pp. 95-106.

APA

Spinks, D., Torrie, L. S., Thompson, S., Harrison, J. R., Frearson, J. A., Read, K. D., Fairlamb, A. H., Wyatt, P. G., & Gilbert, I. H. (2012). Design, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors. ChemMedChem, 7(1), 95-106doi: 10.1002/cmdc.201100420

Vancouver

Spinks D, Torrie LS, Thompson S, Harrison JR, Frearson JA, Read KD et al. Design, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors. ChemMedChem. 2012 Jan 2;7(1):95-106.

Author

Spinks, Daniel; Torrie, Leah S.; Thompson, Stephen; Harrison, Justin R.; Frearson, Julie A.; Read, Kevin D.; Fairlamb, Alan H.; Wyatt, Paul G.; Gilbert, Ian H. / Design, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors.

In: ChemMedChem, Vol. 7, No. 1, 02.01.2012, p. 95-106.

Research output: Contribution to journalArticle

Bibtex - Download

@article{83384ce4dec44ae5bd56ad518664a6d2,
title = "Design, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors",
author = "Daniel Spinks and Torrie, {Leah S.} and Stephen Thompson and Harrison, {Justin R.} and Frearson, {Julie A.} and Read, {Kevin D.} and Fairlamb, {Alan H.} and Wyatt, {Paul G.} and Gilbert, {Ian H.}",
year = "2012",
volume = "7",
number = "1",
pages = "95--106",
journal = "ChemMedChem",
issn = "1860-7179",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Design, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors

A1 - Spinks,Daniel

A1 - Torrie,Leah S.

A1 - Thompson,Stephen

A1 - Harrison,Justin R.

A1 - Frearson,Julie A.

A1 - Read,Kevin D.

A1 - Fairlamb,Alan H.

A1 - Wyatt,Paul G.

A1 - Gilbert,Ian H.

AU - Spinks,Daniel

AU - Torrie,Leah S.

AU - Thompson,Stephen

AU - Harrison,Justin R.

AU - Frearson,Julie A.

AU - Read,Kevin D.

AU - Fairlamb,Alan H.

AU - Wyatt,Paul G.

AU - Gilbert,Ian H.

PY - 2012/1/2

Y1 - 2012/1/2

N2 - <p>Trypanothione synthetase (TryS) is essential for the survival of the protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis. It is one of only a handful of chemically validated targets for T. brucei in vivo. To identify novel inhibitors of TbTryS we screened our in-house diverse compound library that contains 62?000 compounds. This resulted in the identification of six novel hit series of TbTryS inhibitors. Herein we describe the SAR exploration of these hit series, which gave rise to one common series with potency against the enzyme target. Cellular studies on these inhibitors confirmed on-target activity, and the compounds have proven to be very useful tools for further study of the trypanothione pathway in kinetoplastids.</p>

AB - <p>Trypanothione synthetase (TryS) is essential for the survival of the protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis. It is one of only a handful of chemically validated targets for T. brucei in vivo. To identify novel inhibitors of TbTryS we screened our in-house diverse compound library that contains 62?000 compounds. This resulted in the identification of six novel hit series of TbTryS inhibitors. Herein we describe the SAR exploration of these hit series, which gave rise to one common series with potency against the enzyme target. Cellular studies on these inhibitors confirmed on-target activity, and the compounds have proven to be very useful tools for further study of the trypanothione pathway in kinetoplastids.</p>

KW - antiprotozoal agents

KW - drug design

KW - Trypanosoma brucei

KW - trypanothione synthetase

KW - HUMAN AFRICAN TRYPANOSOMIASIS

KW - DRUG TARGET

KW - METABOLISM

KW - REDUCTASE

KW - BIOSYNTHESIS

KW - LEISHMANIA

KW - LEAD

UR - http://ukpmc.ac.uk/articles/PMC3320663

U2 - 10.1002/cmdc.201100420

DO - 10.1002/cmdc.201100420

M1 - Article

JO - ChemMedChem

JF - ChemMedChem

SN - 1860-7179

IS - 1

VL - 7

SP - 95

EP - 106

ER -

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