Nucleosides, nucleotides and nucleic acids

Abstract

ABSTRACT Purine antimetabolites have been very successful therapeutic agents against a host ofinfectious diseases and malignancies. Success of the treatment relies as much on theefficient accumulation by the target cell or organism as it does on selective action on avital biochemical pathway of the target cell. Here we compare the ability of a newclass of tricyclic purine antimetabolites to interact with transporters from humanerythrocytes or Trypanosoma brucei . We show that these compounds display aremarkable selectivity for the parasite’s transporters. The adenine analogue showedgreater trypanocidal activity than the hypoxanthine or guanine analogues in vitro.Key Words: Trypanosoma brucei; Purine antimetabolite; Purine transporter; Druguptake; Drug selectivity. # This work was funded by the Wellcome Trust. Current Address: University of Maryland, Baltimore County, Baltimore, MD, USA.*Correspondence: H. P. de Koning, Institute of Biomedical and Life Sciences, Division ofInfection and Immunity, University of Glasgow, Glasgow G12 8QQ, UK.1441