title: Novel functionalized melamine-based nitroheterocycles: synthesis and activity against trypanosomatid parasites.
abstract: Human African trypanosomiasis (HAT), caused by the protozoan parasite Trypanosoma brucei spp., is a major health problem in sub-Saharan Africa. New drugs are urgently required for the disease. Selective uptake of toxic compounds into trypanosomes has been achieved by exploiting plasma membrane transporters. For example, the P2 aminopurine transporter, along with other transporters, selectively concentrates melamine and benzamidine moieties into trypanosomes. We have previously reported the use of the melamine motif to selectively target nitrofuran to the trypanosome. In this paper we report the further investigation of the structure activity relationships and the effect of the introduction of different functionalized substituents onto the melamine unit. Most of the compounds tested in vitro for their trypanocidal activity showed activities in the submicromolar range against T. b. rhodesiense.
authors.affiliation: School of Life Sciences, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee, DD1 5EH, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Baliani
authors.forename: Valerie
authors.initials: V
authors.lastname: Peal
authors.forename: Ludovic
authors.initials: L
authors.lastname: Gros
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.forename: Michael P
authors.initials: MP
authors.lastname: Barrett
authors.forename: Ian H
authors.initials: IH
authors.lastname: Gilbert
mesh_terms: D000818:Animals; D002460:Cell Line; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects*
chemical_list: D006571:Heterocyclic Compounds; D009574:Nitro Compounds; D014227:Triazines; D014344:Trypanocidal Agents; C011907:melamine