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.

Melamine conjugates of DFMO, fluoroquinolones and artesunate designed for selective uptake by Trypanosoma brucei.Figure optionsDownload as PowerPoint slide