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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 EC(50) 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.

SUBMITTER: Smith VC

PROVIDER: S-EPMC3229842 | biostudies-other | 2011 Oct

REPOSITORIES: biostudies-other

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Optimisation of the anti-Trypanosoma brucei activity of the opioid agonist U50488.

Smith Victoria C VC Cleghorn Laura A T LA Woodland Andrew A Spinks Daniel D Hallyburton Irene I Collie Iain T IT Mok N Yi NY Norval Suzanne S Brenk Ruth R Fairlamb Alan H AH Frearson Julie A JA Read Kevin D KD Gilbert Ian H IH Wyatt Paul G PG

ChemMedChem 20110810 10

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 EC(50) value of 59 nM as determined in our T. brucei in vitro assay reported previously. This paper describes the modification of key structura ...[more]

PMID: 21834094

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