Effect of allopurinol on Trypanosoma cruzi: metabolism and biological activity in intracellular and bloodstream forms

Allopurinol (4-hydroxypyrazolo [3,4-d]pyrimidine) is an effective agent in vitro against Trypanosoma cruzi. The important forms of this parasite, with respect to the pathogenesis of Chagas' disease in man, are the bloodstream (trypomastigote) and the intracellular forms. Experiments with radiolabeled allopurinol and analysis of the metabolic products of this compound by high-performance liquid chromatography showed that both the bloodstream and the intracellular forms of T. cruzi metabolize allopurinol in the same manner as has been shown for the epimastigotes in vitro. The metabolic pathways for pyrazolopyrimidines in the pathogenic forms were demonstrated with organisms isolated from infected animals and a tissue culture system infected with T. cruzi. Treatment of infected tissue culture with allopurinol eradicated the infection. This investigation implies that allopurinol may be useful in chemotherapy of T. cruzi infections, a supposition which has been borne out in one animal study.