Pyrazolopyrimidine Metabolism in Parasitic Protozoa

The pyrazolopyrimidines are purine analogs that are cytotoxic toward and metabolized by several genera of parasitic protozoa, including the Leishmania and the Trypanosoma. Examples of pyrazolopyrimidines that are selectively metabolized by these parasites include allopurinol, allopurinol riboside, 4-thiopurinol, 4-thiopurinol riboside, and formycin B. These pathogenic protozoa are capable of efficient conversion of the pyrazolopyrimidines to the nucleotide level. The pyrazolopyrimidine metabolites which are isomers of inosine monophosphate are subsequently aminated and incorporated as the adenylate analog into RNA. Mammalian cells are incapable of these metabolic transformations. The sulfur containing pyrazolopyrimidines, however, are neither aminated nor incorporated into nucleic acid. The selective metabolism of the pyrazolopyrimidines by the intracellular metabolic machinery of the parasites of the Trypanosomatidae family offers a rational approach to the chemotherapy of the diseases caused by these pathogenic hemoflagellates.