Standard
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 journal › Article
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. DOI:
10.1002/cmdc.201100420APA
Spinks, D., Torrie, L. S., Thompson, S., Harrison, J. R., Frearson, J. A., Read, K. D.
, ... Gilbert, I. H. (2012).
Design, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors.
ChemMedChem,
7(1), 95-106. DOI:
10.1002/cmdc.201100420Vancouver
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. Available from, DOI:
10.1002/cmdc.201100420Author
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 journal › Article
@article{83384ce4dec44ae5bd56ad518664a6d2,
title = "Design, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors",
abstract = "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.",
keywords = "antiprotozoal agents, drug design, Trypanosoma brucei, trypanothione synthetase, HUMAN AFRICAN TRYPANOSOMIASIS, DRUG TARGET, METABOLISM, REDUCTASE, BIOSYNTHESIS, LEISHMANIA, LEAD",
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",
month = "1",
doi = "10.1002/cmdc.201100420",
volume = "7",
pages = "95--106",
journal = "ChemMedChem",
issn = "1860-7179",
publisher = "Wiley-VCH",
number = "1",
}
RIS (suitable for import to EndNote) - Download
TY - JOUR
T1 - Design, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors
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 - 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.
AB - 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.
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
U2 - 10.1002/cmdc.201100420
DO - 10.1002/cmdc.201100420
M3 - Article
VL - 7
SP - 95
EP - 106
JO - ChemMedChem
T2 - ChemMedChem
JF - ChemMedChem
SN - 1860-7179
IS - 1
ER -