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

J Med Chem. 2001 Oct 11;44(21):3440-52. doi: 10.1021/jm010854+.


The P2 transporter is a nucleoside transporter which is unique to the protozoan parasite Trypanosoma brucei, the causative organism of Human African Trypanosomasis. The transporter has been shown to bind some structural motifs not recognized by other transporters. In this paper we describe the use of the melamine motif, a substrate of the P2 transporter, as a potential tool to selectively deliver polyamine analogues to the parasites. The synthesis of a number of polyamine analogues attached to a variety of melamine analogues is described. Many of the compounds were shown to competitively inhibit uptake of adenosine, indicating that they are recognized by the transporter. Some of the compounds showed good in vitro activity against the parasites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism
  • Animals
  • Biological Transport
  • Carrier Proteins / metabolism
  • Cell Line
  • Polyamines / chemical synthesis*
  • Polyamines / chemistry
  • Polyamines / pharmacology
  • Protozoan Proteins / metabolism
  • Rats
  • Structure-Activity Relationship
  • Triazines / chemical synthesis*
  • Triazines / chemistry
  • Triazines / pharmacology
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology
  • Trypanosoma brucei brucei / drug effects
  • Trypanosoma brucei brucei / metabolism
  • Trypanosoma cruzi / drug effects


  • Carrier Proteins
  • Polyamines
  • Protozoan Proteins
  • Triazines
  • Trypanocidal Agents
  • Adenosine