title: Selective delivery of 2-hydroxy APA to Trypanosoma brucei using the melamine motif.
abstract: Trypanosoma brucei, the parasite that causes human African trypanosomiasis, is auxotrophic for purines and has specialist nucleoside transporters to import these metabolites. In particular, the P2 aminopurine transporter can also selectively accumulate melamine derivatives. In this Letter, we report the coupling of the melamine moiety to 2-hydroxy APA, a potent ornithine decarboxylase inhibitor, with the aim of selectively delivering this compound to the parasite. The best compound described here shows an increased in vitro trypanocidal activity compared with the parent.
authors.affiliation: Division of Biological Chemistry and Drug Discovery, College of Life Science, University of Dundee, Sir James Black Centre, Dundee, UK.
authors.forename: Nina
authors.initials: N
authors.lastname: Klee
authors.forename: Pui Ee
authors.initials: PE
authors.lastname: Wong
authors.forename: Beatriz
authors.initials: B
authors.lastname: Baragaña
authors.forename: Farah El
authors.initials: FE
authors.lastname: Mazouni
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Phillips
authors.forename: Michael P
authors.initials: MP
authors.lastname: Barrett
authors.forename: Ian H
authors.initials: IH
authors.lastname: Gilbert
mesh_terms: D006801:Humans; D009955:Ornithine Decarboxylase / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D011437:Propylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy
chemical_list: C553246:2-hydroxy-(aminooxy)propanamine; D065108:Ornithine Decarboxylase Inhibitors; D011437:Propylamines; D014227:Triazines; D014344:Trypanocidal Agents; D009955:Ornithine Decarboxylase; C011907:melamine