Efficacy of pyrazolopyrimidine ribonucleosides against Trypanosoma cruzi: studies in vitro and in vivo with sensitive and resistant strains.

R L Berens, J J Marr, D L Looker, D J Nelson, S W LaFon

Index: J. Infect. Dis. 150(4) , 602-8, (1984)

Full Text: HTML

Abstract

Strains of Trypanosoma cruzi differ in their susceptibilities to and metabolism of pyrazolopyrimidines. Allopurinol riboside can control but not eliminate infections with a sensitive strain in both tissue culture and mice. Formycin B, which proved to be greater than 10-fold more effective on a weight basis, showed a similar strain specificity but could eliminate an infection with a sensitive strain from tissue culture. However, this drug, unlike allopurinol riboside, was converted to toxic analogues of adenosine mono-, di-, and triphosphate by uninfected tissue culture cells. Thiopurinol and its riboside were effective against all strains unless culture was performed in purine-defined medium. Thus formycin B and allopurinol riboside appear to be good models for the design of antitrypanosomal agents. Suitable modification of the molecule may provide an effective chemotherapeutic agent.