title: Efficacy of pyrazolopyrimidine ribonucleosides against Trypanosoma cruzi: studies in vitro and in vivo with sensitive and resistant strains.
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.
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000493:Allopurinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014355:Chagas Disease / Q000188:drug therapy; D004351:Drug Resistance; D005573:Formycins / Q000378:metabolism / Q000494:pharmacology; D007288:Inosine / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D012263:Ribonucleosides / Q000494:pharmacology*; D013872:Thionucleosides / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D005573:Formycins; D012263:Ribonucleosides; D013872:Thionucleosides; C034561:formycin B; C004420:4-aminopyrazolo(3,4-d)pyrimidine; C033494:thiopurinol ribonucleoside; D007288:Inosine; D000493:Allopurinol; C005832:tisopurine; D000225:Adenine; C021958:allopurinol riboside