EFFICACY OF PYRAZOLOPYRIMIDINE RIBONUCLEOSIDES AGAINST TRYPANOSOMA-CRUZI - STUDIES INVITRO AND INVIVO WITH SENSITIVE AND RESISTANT STRAINS

Strains of T. 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 > 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. This drug, unlike allopurinol riboside, was converted to toxic analogs 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.