Synthesis and biological evaluation of s-triazine substituted polyamines as potential new anti-trypanosomal drugs

The P2 transporter is a nucleoside transporter which is unique to the proto zoan parasite Trypanosoma brucei, the causative organism of Human African T rypanosomasis. The transporter has been shown to bind some structural motif s not recognized by other transporters. In this paper we describe the use o f the melamine motif, a substrate of the P2 transporter, as a potential too l to selectively deliver polyamine analogues to the parasites. The synthesi s of a number of polyamine analogues attached to a variety of melamine anal ogues is described. Many of the compounds were shown to competitively inhib it uptake of adenosine, indicating that they are recognized by the transpor ter. Some of the compounds showed good in vitro activity against the parasi tes.