Action of pyrazolopyrimidine derivatives on American Leishmania spp. promastigotes.
The capacity of 54 different pyrazolo-(3,4-d)- or -(4,3-d)-pyrimidine derivatives to inhibit American Leishmania promastigote multiplication was evaluated. Among pyrazolo-(3,4-d)-pyrimidines, eight derivatives showed leishmanistatic activity, 4-aminopyrazolo-(3,4-d)-pyrimidine (APP) being the most active, about eight-fold more than 4-hydroxy-pyrazolo-(3,4-d)-pyrimidine (HPP). 7-Hydroxy-3-beta-D-ribofuranosylpyrazolo-(4,3-d)-pyrimidine (FoB) was as active as 7-amino-3-beta-D-ribofuranosylpyrazolo-(4,3-d)-pyrimidine (FoA), a situation different to that found for pyrazolo-(3,4-d)-pyrimidines. Furthermore, different chemical modifications in formycin structure did not modify inhibitory effects. It can be concluded that regarding American Leishmania the chemical analogy to hypoxanthine or inosine of pyrazolo-(3,4-d)- and pyrazolo-(4,3-d)-pyrimidine, respectively, is not absolutely critical, as different modifications on the heterocyclic ring did not abolish the inhibitory activity of these compounds.
Avila
J L
JL
Polegre
M A
MA
Avila
A
A
Robins
R K
RK
D000818:Animals; D007891:Leishmania / Q000187:drug effects*; D011743:Pyrimidines / Q000494:pharmacology*; D012556:Schistosomicides / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011743:Pyrimidines; D012556:Schistosomicides