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Bioorg Med Chem. 2012 Feb 15;20(4):1607-15. Epub 2011 Dec 27.

Quinol derivatives as potential trypanocidal agents.

Capes A, Patterson S, Wyllie S, Hallyburton I, Collie IT, McCarroll AJ, Stevens MF, Frearson JA, Wyatt PG, Fairlamb AH, Gilbert IH.

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Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

Abstract

Quinols have been developed as a class of potential anti-cancer compounds. They are thought to act as double Michael acceptors, forming two covalent bonds to their target protein(s). Quinols have also been shown to have activity against the parasite Trypanosoma brucei, the causative organism of human African trypanosomiasis, but they demonstrated little selectivity over mammalian MRC5 cells in a counter-screen. In this paper, we report screening of further examples of quinols against T. brucei. We were able to derive an SAR, but the compounds demonstrated little selectivity over MRC5 cells. In an approach to increase selectivity, we attached melamine and benzamidine motifs to the quinols, because these moieties are known to be selectively concentrated in the parasite by transporter proteins. In general these transporter motif-containing analogues showed increased selectivity; however they also showed reduced levels of potency against T. brucei.

Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID:: 22264753; [PubMed - in process]
PMCID:: PMC3281193

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