Targeted delivery of compounds to Trypanosoma brucei using the melamine motif.
There is an urgent need for the development of new drugs for the treatment of human African trypanosomiasis. The causative organism, Trypanosoma brucei, has been shown to have some unusual plasma membrane transporters, in particular the P2 aminopurine transporter and related permeases, which have been used for the selective targeting of trypanocidal compounds to the organism. In this paper, we report the addition of melamine-based P2-targeting motifs to three different classes of compound in order to try and improve activity through increased selective uptake. The classes reported here are fluoroquinolones, difluoromethylornithine and artesunate derivatives.
Chollet
Constance
C
Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee DD1 5EH, UK.
Baliani
Alessandro
A
Wong
Pui Ee
PE
Barrett
Michael P
MP
Gilbert
Ian H
IH
D000818:Animals; D000518:Eflornithine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D014227:Triazines / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
D014227:Triazines; D014344:Trypanocidal Agents; C011907:melamine; D000518:Eflornithine