Optimisation of the Anti-Trypanosoma brucei Activity of the Opioid Agonist U50488. / Smith, Victoria C.; Cleghorn, Laura A. T.; Woodland, Andrew; Spinks, Daniel; Hallyburton, Irene; Collie, Iain T.; Mok, N. Yi; Norval, Suzanne; Brenk, Ruth; Fairlamb, Alan H.; Frearson, Julie A.; Read, Kevin D.; Gilbert, Ian H.; Wyatt, Paul G.
In: ChemMedChem, Vol. 6, No. 10, 04.10.2011, p. 1832-1840.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Optimisation of the Anti-Trypanosoma brucei Activity of the Opioid Agonist U50488
A1 - Smith,Victoria C.
A1 - Cleghorn,Laura A. T.
A1 - Woodland,Andrew
A1 - Spinks,Daniel
A1 - Hallyburton,Irene
A1 - Collie,Iain T.
A1 - Mok,N. Yi
A1 - Norval,Suzanne
A1 - Brenk,Ruth
A1 - Fairlamb,Alan H.
A1 - Frearson,Julie A.
A1 - Read,Kevin D.
A1 - Gilbert,Ian H.
A1 - Wyatt,Paul G.
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
Y1 - 2011/10/4
N2 - <p>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.</p>
AB - <p>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.</p>
KW - antiprotozoal agents
KW - human African trypanosomiasis
KW - medicinal chemistry
KW - U50488
KW - HUMAN AFRICAN TRYPANOSOMIASIS
KW - DERIVATIVES
KW - DISEASES
UR - http://ukpmc.ac.uk/articles/PMC3229842
U2 - 10.1002/cmdc.201100278
DO - 10.1002/cmdc.201100278
M1 - Article
JO - ChemMedChem
JF - ChemMedChem
SN - 1860-7179
IS - 10
VL - 6
SP - 1832
EP - 1840
ER -
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