PURINE ANALOGS AS CHEMOTHERAPEUTIC-AGENTS IN LEISHMANIASIS AND AMERICAN TRYPANOSOMIASIS

The metabolic pathways for purines in parasitic protozoans differ significantly from the corresponding pathways in human beings. Leishmania and Trypanosoma cruzi have particular enzymatic reactions that have relevance for chemotherapy. Certain purine analogs are metabolized by the parasites to nucleotides and aminated to the analogs of adenine nucleotides. These halt protein synthesis and cause the breakdown of RNA. The most important purine analogs with respect to chemotherapeutic potential are the pyrazolo [3,4-D]-pyrimidines. The prototype, allopurinol, is nontoxic to human beings and is aminated to adenine nucleotide analogs by the organism. Studies in vitro and in vivo have demonstrated its antiparasitic action and led to its development as a chemotherapeutic agent for diseases caused by these organisms. Clinical investigations now have demonstrated the therapeutic efficacy of allopurinol in cutaneous leishmaniasis caused by Leishmania braziliensis and in chronic Chagas' Disease.