Novel functionalized melamine-based nitroheterocycles: synthesis and activity against trypanosomatid parasites.
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.
Baliani
Alessandro
A
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.
Peal
Valerie
V
Gros
Ludovic
L
Brun
Reto
R
Kaiser
Marcel
M
Barrett
Michael P
MP
Gilbert
Ian H
IH
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*
D006571:Heterocyclic Compounds; D009574:Nitro Compounds; D014227:Triazines; D014344:Trypanocidal Agents; C011907:melamine