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