Selective Transport of a New Class of Purine Antimetabolites by the Protozoan Parasite Trypanosoma brucei

• Published in: Nucleosides, nucleotides & nucleic acids Vol. 23; no. 8-9; pp. 1441 - 1444
• Main Authors: Wallace, L. J. M., Candlish, D., Hagos, A., Seley, K. L., de Koning, H. P.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis Group 01.10.2004
• Subjects: Allopurinol - pharmacology; Animals; Antimetabolites - chemical synthesis; Antimetabolites - metabolism; Biological Transport; Dose-Response Relationship, Drug; Drug selectivity; Drug uptake; Erythrocytes - metabolism; Humans; Kinetics; Models, Chemical; Nucleobase Transport Proteins - chemistry; Oxazines - pharmacology; Purine antimetabolite; Purine transporter; Purines - chemistry; Purines - metabolism; Rats; Trypanosoma brucei; Trypanosoma brucei brucei; Xanthenes - pharmacology
• ISSN: 1525-7770; 1532-2335
• DOI: 10.1081/NCN-200027660

Purine antimetabolites have been very successful therapeutic agents against a host of infectious diseases and malignancies. Success of the treatment relies as much on the efficient accumulation by the target cell or organism as it does on selective action on a vital biochemical pathway of the target cell. Here we compare the ability of a new class of tricyclic purine antimetabolites to interact with transporters from human erythrocytes or Trypanosoma brucei. We show that these compounds display a remarkable selectivity for the parasite's transporters. The adenine analogue showed greater trypanocidal activity than the hypoxanthine or guanine analogues in vitro. # This work was funded by the Wellcome Trust.