Optimisation of the Anti-Trypanosoma brucei Activity of the Opioid Agonist U50488

Victoria C. Smith; Laura A. T. Cleghorn; Andrew Woodland; Daniel Spinks; Irene Hallyburton; Iain T. Collie; N. Yi Mok; Suzanne Norval; Ruth Brenk; Alan H. Fairlamb; Julie A. Frearson; Kevin D. Read; Ian H. Gilbert; Paul G. Wyatt

doi:10.1002/cmdc.201100278

Optimisation of the Anti-Trypanosoma brucei Activity of the Opioid Agonist U50488

Victoria C. Smith, Laura A. T. Cleghorn, Andrew Woodland, Daniel Spinks, Irene Hallyburton, Iain T. Collie, N. Yi Mok, Suzanne Norval, Ruth Brenk, Alan H. Fairlamb, Julie A. Frearson, Kevin D. Read, Ian H. Gilbert, Paul G. Wyatt

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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Abstract

Screening of the Sigma-Aldrich Library of Pharmacologically Active Compounds (LOPAC) against cultured Trypanosoma brucei, the causative agent of African sleeping sickness, resulted in the identification of a number of compounds with selective antiproliferative activity over mammalian cells. These included (+)-(1R,2R)-U50488, a weak opioid agonist with an EC50 value of 59 nm as determined in our T. brucei in vitro assay reported previously. This paper describes the modification of key structural elements of U50488 to investigate structure-activity relationships (SAR) and to optimise the antiproliferative activity and pharmacokinetic properties of this compound.

Original language	English
Pages (from-to)	1832-1840
Number of pages	9
Journal	ChemMedChem
Volume	6
Issue number	10
DOIs	https://doi.org/10.1002/cmdc.201100278
Publication status	Published - 4 Oct 2011

Keywords

antiprotozoal agents
human African trypanosomiasis
medicinal chemistry
U50488
HUMAN AFRICAN TRYPANOSOMIASIS
DERIVATIVES
DISEASES

UN SDGs

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

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10.1002/cmdc.201100278

http://ukpmc.ac.uk/articles/PMC3229842

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Embargo ends: 31/12/99

Aref#d: 18185. Characterization and validation of drug targets in the Kinetoplastida (Principal Research Fellowship/Programme Grant)
Fairlamb, A. (Investigator)
1/10/06 → 30/09/17
Project: Research

Cite this

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title = "Optimisation of the Anti-Trypanosoma brucei Activity of the Opioid Agonist U50488",

abstract = "Screening of the Sigma-Aldrich Library of Pharmacologically Active Compounds (LOPAC) against cultured Trypanosoma brucei, the causative agent of African sleeping sickness, resulted in the identification of a number of compounds with selective antiproliferative activity over mammalian cells. These included (+)-(1R,2R)-U50488, a weak opioid agonist with an EC50 value of 59 nm as determined in our T. brucei in vitro assay reported previously. This paper describes the modification of key structural elements of U50488 to investigate structure-activity relationships (SAR) and to optimise the antiproliferative activity and pharmacokinetic properties of this compound.",

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author = "Smith, {Victoria C.} and Cleghorn, {Laura A. T.} and Andrew Woodland and Daniel Spinks and Irene Hallyburton and Collie, {Iain T.} and Mok, {N. Yi} and Suzanne Norval and Ruth Brenk and Fairlamb, {Alan H.} and Frearson, {Julie A.} and Read, {Kevin D.} and Gilbert, {Ian H.} and Wyatt, {Paul G.}",

year = "2011",

month = oct,

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doi = "10.1002/cmdc.201100278",

language = "English",

volume = "6",

pages = "1832--1840",

journal = "ChemMedChem",

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AU - Smith, Victoria C.

AU - Cleghorn, Laura A. T.

AU - Woodland, Andrew

AU - Spinks, Daniel

AU - Hallyburton, Irene

AU - Collie, Iain T.

AU - Mok, N. Yi

AU - Norval, Suzanne

AU - Brenk, Ruth

AU - Fairlamb, Alan H.

AU - Frearson, Julie A.

AU - Read, Kevin D.

AU - Gilbert, Ian H.

AU - Wyatt, Paul G.

PY - 2011/10/4

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AB - Screening of the Sigma-Aldrich Library of Pharmacologically Active Compounds (LOPAC) against cultured Trypanosoma brucei, the causative agent of African sleeping sickness, resulted in the identification of a number of compounds with selective antiproliferative activity over mammalian cells. These included (+)-(1R,2R)-U50488, a weak opioid agonist with an EC50 value of 59 nm as determined in our T. brucei in vitro assay reported previously. This paper describes the modification of key structural elements of U50488 to investigate structure-activity relationships (SAR) and to optimise the antiproliferative activity and pharmacokinetic properties of this compound.

KW - antiprotozoal agents

KW - human African trypanosomiasis

KW - medicinal chemistry

KW - U50488

KW - HUMAN AFRICAN TRYPANOSOMIASIS

KW - DERIVATIVES

KW - DISEASES

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DO - 10.1002/cmdc.201100278

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JO - ChemMedChem

JF - ChemMedChem

IS - 10

ER -

Optimisation of the Anti-Trypanosoma brucei Activity of the Opioid Agonist U50488

Abstract

Keywords

UN SDGs

Access to Document

Embargoed Document

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Projects

Aref#d: 18185. Characterization and validation of drug targets in the Kinetoplastida (Principal Research Fellowship/Programme Grant)

Cite this