title: Quinol derivatives as potential trypanocidal agents.
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.
authors.affiliation: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Capes
authors.forename: Stephen
authors.initials: S
authors.lastname: Patterson
authors.forename: Susan
authors.initials: S
authors.lastname: Wyllie
authors.forename: Irene
authors.initials: I
authors.lastname: Hallyburton
authors.forename: Iain T
authors.initials: IT
authors.lastname: Collie
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McCarroll
authors.forename: Malcolm F G
authors.initials: MF
authors.lastname: Stevens
authors.forename: Julie A
authors.initials: JA
authors.lastname: Frearson
authors.forename: Paul G
authors.initials: PG
authors.lastname: Wyatt
authors.forename: Alan H
authors.initials: AH
authors.lastname: Fairlamb
authors.forename: Ian H
authors.initials: IH
authors.lastname: Gilbert
mesh_terms: D001550:Benzamidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D016503:Drug Delivery Systems; D006801:Humans; D006873:Hydroquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
chemical_list: D001550:Benzamidines; D006873:Hydroquinones; D014227:Triazines; D014344:Trypanocidal Agents; C032157:benzamidine; C011907:melamine