Biological action of pyrazolopyrimidine derivatives against Trypanosoma cruzi. Studies in vitro and in vivo.
The capacity of 54 different pyrazolo(3,4-d) or (4,3-d)pyrimidine derivatives to inhibit Trypanosoma cruzi epimastigote and trypomastigote multiplication, and for some of them its chemotherapeutic activity, was evaluated. Six pyrazolo(3,4-d)pyrimidines showed inhibitory activity against epimastigote forms, 4-aminopyrazolo(3,4-d)pyrimidine being the most active, 5-fold more so than 4-hydroxypyrazolo(3,4-d)-pyrimidine. Neither compound was active against freshly isolated trypomastigotes, suggesting biochemical differences between culture and bloodstream forms of T. cruzi. On both epimastigote and trypomastigote forms, 7-amino-3-beta-D-ribofuranosylpyrazolo-(4,3-d)pyrimidine (FoA) was about 2-fold more active than 7-hydroxy-3-beta-D-ribofuranosylpyrazolo-(4,3-d)pyrimidine (FoB); however, when tested on T. cruzi-infected mice, only FoB exhibited significant chemotherapeutic activity. Previous results suggest that, except for FoB and FoA: (a) pyrazolopyrimidine insensitivity is trypomastigote-specific and (b) drug-insensitivity is lost when trypomastigotes transform into epimastigotes and vice versa.
D000818:Animals; D014355:Chagas Disease / Q000097:blood / Q000188:drug therapy; D051379:Mice; D011743:Pyrimidines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents; D014349:Trypanosoma cruzi / Q000187:drug effects*
D011743:Pyrimidines; D014344:Trypanocidal Agents