Loading…

Quinol derivatives as potential trypanocidal agents

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 huma...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2012-02, Vol.20 (4), p.1607-1615
Main Authors: Capes, Amy, Patterson, Stephen, Wyllie, Susan, Hallyburton, Irene, Collie, Iain T., McCarroll, Andrew J., Stevens, Malcolm F.G., Frearson, Julie A., Wyatt, Paul G., Fairlamb, Alan H., Gilbert, Ian H.
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2011.12.018