Pyrazolopyrimidine metabolism in parasitic protozoa

Buddy Ullman

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Abstract

The sensitivities of the pathogenic hemoflagellates to the pyrazolopyrimidines offer a rational approach to the treatment of leishmaniasis and trypanosomiasis The response of these parasitic protozoa to pyrazolopyrimidines results from the selective capacity of these organisms to accumulate the purine analogs to the nucleotide level. The unique purine salvage enzymes, particularly the hypoxanthine-guanine phosphoribosyltransferase, the adenylosuccinate synthetase, and the nucleoside phosphotransferase, appear to play important roles in the selective metabolism of the pyrazolopyrimidines in parasites. HPP has proved to be efficaceous in the eradication of leishmaniasis in mice and monkeys, and in the treatment of Chagas disease in mice. As well, HPP was useful in the treatment of antimony-resistant visceral leishmanasis in 4 of 6 patients. Other pyrazolopyrimidine analogs are currently undergoing toxicological and phase I clinical studies. The overall chemotherapeutic potential of the pyrazolopyrimidine analogs of purine nucleobases and nucleosides remains an untested yet promising approach to the treatment of these devastating parasitic diseases.

Original languageEnglish (US)
Pages (from-to)194-203
Number of pages10
JournalPharmaceutical Research
VolumeNO. 5
Publication statusPublished - 1984

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ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

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