Pyrazolopyrimidine metabolism in parasitic protozoa

Buddy Ullman

Research output: Contribution to journalArticle

25 Citations (Scopus)

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
StatePublished - 1984

Fingerprint

Protozoa
nucleoside phosphotransferase
Metabolism
Adenylosuccinate Synthase
Purine Nucleosides
Hypoxanthine Phosphoribosyltransferase
Antimony
Salvaging
Leishmaniasis
Nucleotides
Parasitic Diseases
Trypanosomiasis
Chagas Disease
Enzymes
Therapeutics
Toxicology
Haplorhini
Parasites
purine
N-(4'-fluorobutyrophenone)-4-(4-chlorophenyl)pyridinium

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

Pyrazolopyrimidine metabolism in parasitic protozoa. / Ullman, Buddy.

In: Pharmaceutical Research, Vol. NO. 5, 1984, p. 194-203.

Research output: Contribution to journalArticle

Ullman, Buddy. / Pyrazolopyrimidine metabolism in parasitic protozoa. In: Pharmaceutical Research. 1984 ; Vol. NO. 5. pp. 194-203.
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