Advertisement

Comparative Metabolism of a New Antileishmanial Agent, Allopurinol Riboside, in the Parasite and the Host Cell

  • Donald J. Nelson
  • Stephen W. LaFon
  • Gertrude B. Elion
  • J. Joseph Marr
  • Randolph L. Berens
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 122B)

Abstract

Leishmania donovani and L. braziliensis are monocellular hemoflagellates which infect millions of people in tropical regions of the world. These parasitic organisms depend exclusively upon salvage of bases and nucleosides from the host mileu for their purine requirement1. Allopurinol (HPP) as well as 4-aminopyrazolo(3,4-d)pyrimidine (4-APP) and oxipurinol (DHPP) are inhibitors of the growth of the promastigote form of these organisms in culture and adenine can reverse this effect2. Since HPP is a widely used therapeutic agent for the control of hyperuricemia in man and is remarkably non-toxic to mammalian cells, it was of interest to determine how the metabolism of HPP and allopurinol riboside (HPP-Rib), a normal metabolite of allopurinol in man3, differs in the leishmaniae and mammalian host.

Keywords

Purine Nucleoside Purine Nucleoside Phosphorylase Hypoxanthine Phosphoribosyltransferase Leishmania Donovani Parasitic Organism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    J. J. Marr, R. L. Berens, and D. J. Nelson, Biochem. Biophys. Acta 544:360 (1978).PubMedCrossRefGoogle Scholar
  2. 2.
    J. J. Marr and R. L. Berens, J. Inf. Disease 136:724 (1977).CrossRefGoogle Scholar
  3. 3.
    G. B. Elion, A. Kovensky and G. H. Hitchings, Biochem. Pharmacol. 15:863 (1966).PubMedCrossRefGoogle Scholar
  4. 4.
    D. J. Nelson, C. J. L. Bugge, G. B. Elion, R. L. Berens and J. J. Marr, J. Biol. Chem. in press.Google Scholar
  5. 5.
    G. B. Elion, F. M. Benezra, I. Canellas, L. O. Carrington and G. H. Hitchings, Israel J. Chem. 6:787 (1968).Google Scholar
  6. 6.
    T. A. Krenitsky, S. M. Niel, G. B. Elion and G. H. Hitchings, Arch. Biochem. Biophys. 150:585 (1972).PubMedCrossRefGoogle Scholar
  7. 7.
    T. A. Krenitsky, G. B. Elion, R. A. Strelitz and G. H. Hitchings, J. Biol. Chem. 242:2675 (1967).PubMedGoogle Scholar
  8. 8.
    T. A. Krenitsky, G. W. Koszalka, J. V. Tuttle, D. L. Adamczyk, G. B. Elion and J. J. Marr, These Proceedings.Google Scholar
  9. 9.
    T. Spector and T. Jones, J. Biol. Chem., in press.Google Scholar
  10. 10.
    T. Spector and R. L. Miller, Biochem. Biophys. Acta 445:509 (1976).PubMedCrossRefGoogle Scholar
  11. 11.
    D. J. Nelson, C. J. L. Bugge, H. C. Krasny and G. B. Elion, Biochem. Pharmacol. 22:2003 (1973).PubMedCrossRefGoogle Scholar
  12. 12.
    D. J. Nelson and G. B. Elion, Biochem. Pharmacol. 24:1235 (1975).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • Donald J. Nelson
    • 1
  • Stephen W. LaFon
    • 1
  • Gertrude B. Elion
    • 1
  • J. Joseph Marr
    • 2
  • Randolph L. Berens
    • 2
  1. 1.Wellcome Research LaboratoriesResearch Triangle ParkUSA
  2. 2.Dept. of MedicineSt. Louis UniversitySt. LouisUSA

Personalised recommendations