Comparative Metabolism of a New Antileishmanial Agent, Allopurinol Riboside, in the Parasite and the Host Cell
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.
KeywordsPurine Nucleoside Purine Nucleoside Phosphorylase Hypoxanthine Phosphoribosyltransferase Leishmania Donovani Parasitic Organism
Unable to display preview. Download preview PDF.
- 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.G. B. Elion, F. M. Benezra, I. Canellas, L. O. Carrington and G. H. Hitchings, Israel J. Chem. 6:787 (1968).Google Scholar
- 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.T. Spector and T. Jones, J. Biol. Chem., in press.Google Scholar