Selective transport of a new class of purine antimetabolites by the protozoan parasite Trypanosoma brucei.
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.
Wallace
L J M
LJ
Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, Glasgow, UK.
Candlish
D
D
Hagos
A
A
Seley
K L
KL
de Koning
H P
HP
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000138:chemical synthesis / Q000378:metabolism*; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D033702:Nucleobase Transport Proteins / Q000737:chemistry; D010078:Oxazines / Q000494:pharmacology; D011687:Purines / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D014346:Trypanosoma brucei brucei; D014966:Xanthenes / Q000494:pharmacology
D000963:Antimetabolites; D033702:Nucleobase Transport Proteins; D010078:Oxazines; D011687:Purines; D014966:Xanthenes; C005843:resazurin; D000493:Allopurinol