Pyridoxal Isonicotinoyl Hydrazone (PIH) and Its Analogues: A New Group of Effective Chelators

  • P. Ponka
  • H. M. Schulman
  • J. Edward


Iron, which is involved in many metabolic processes including transport and storage of oxygen and oxidation-reduction reactions is an essential element for all living cells with the one possible exception lactic acid bacilli. However, organisms are not equipped with active excretory systems for iron and, therefore, if excessive amounts of iron get to the organism they accumulate without being excreted. This results in an iron overload which is a common finding in patients with refractory anemias such as thalassemia major, some other hemoglobinopathies and certain other anemias1 – 4. The overload is a consequence of increased iron absorption, but primarily of long-term transfusion therapy. Excess iron accumulates in liver, heart and endocrine glands causing serious dysfunction and death. Excess iron is removed from such patients by administration of chelating agents, primarily desferrioxamine. However, since desferrioxamine is inadequate and expensive, new iron chelating agents are needed5.


Iron Overload Aromatic Aldehyde Refractory Anemia Excess Iron Thalassemia Major 
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  1. 1.
    A. W. Nienhuis, Moderator, Thalassemia major: molecular and clinical aspects, Ann. Intern. Med. 91: 883 (1979)Google Scholar
  2. 2.
    A. Jacobs, The pathology of iron overload, in: “Iron in Biochemistry and Medicine II”, A. Jacobs and M. Worwood, eds., Academic Press, New York, pp. 427–459 (1980).Google Scholar
  3. 3.
    T. H. Bothwell and R. W. Charlton, A general approach to the problems of ifon deficiency and iron overload in the population at large, Seminars Hematol. 19: 54 (1982).Google Scholar
  4. 4.
    A. V. Hoffbrand, Transfusion siderosis and chelation therapy, in: “Iron in Biochemistry and Medicine II”, A. Jacobs and M. Worwood, eds., Academic Press, New York, pp. 499–527 (1980).Google Scholar
  5. 5.
    D. J. Weatherall, M. J. Pippard, and S. F. Callender, Editorial retrospective. Iron loading in thalassemia - five years with the pump, N. Engl. J. Med. 308: 456 (1983).PubMedCrossRefGoogle Scholar
  6. 6.
    P. Ponka, J. Borova, J. Neuwirt, and O. Fuchs, Mobilization of iron from reticulocytes: Identification of pyridoxal isonicotinoyl hydrazone as a new iron chelating agent, FEBS Lett. 97: 317 (1979).PubMedCrossRefGoogle Scholar
  7. 7.
    P. Ponka, J. Borova, J. Neuwirt, 0. Fuchs, and E. Necas, A study of intracellular iron metabolism using pyridoxal isonicotinoyl hydrazone and other synthetic chelating agents, Biochim. Biophys. Acta 586: 278 (1979).Google Scholar
  8. 8.
    A. Huang and P. Ponka, A study of the mechanism of action of pyridoxal isonicotinoyl hydrazone at the cellular level using reticulocytes loaded with non-heme 59Fe, Biochim. Biophys. Acta 757: 306 (1983).CrossRefGoogle Scholar
  9. 9.
    E. H. Morgan, Chelator-mediated iron efflux from reticulocytes. Biochim. Biophys. Acta 733: 39 (1983).CrossRefGoogle Scholar
  10. 10.
    L. Baker, M. L. Vitolo, and J. Webb, Hepatocytes in culture as an in vitro screen for iron chelators: Evaluation of analogues of PIH, in: “Structure and Function of Iron Storage Proteins”, I. Urushizaki, P. Aísen, I. Listowsky, and J. W. Drysdale, eds., Elsevier, pp. 457–460 (1983).Google Scholar
  11. 11.
    M. Cikrt, P. Ponka, E. Necas, and J. Neuwirt, Biliary iron excretion in rats following pyridoxal isonicotinoyl hydrazone, Brit. J. Haematol. 45: 275 (1980).CrossRefGoogle Scholar
  12. 12.
    C. Hershko, C. Avramovici-Grisaru, G. Link, L. Gelfand, and S. Sarei, Mechanism of in vivo iron chelation by pyridoxal isonicotinoyl hydrazone and other imino derivatives of pyridoxal, J. Lab. Clin. Med. 98: 99 (1981).PubMedGoogle Scholar
  13. 13.
    P. Ponka, M. Gauthier, F. L. Chubb, and Edward, T. J., Synthesis and characterization of iron-chelating acylhydrazones derived from pyridoxal isonicotinoyl hydrazone (PIH), J. Chem. Eng. Data, submitted for publication.Google Scholar
  14. 14.
    F. Wild, in: “Characterization of Organic Compounds, 2nd ed.”, Cambridge University Press, p. 110 (1958).Google Scholar
  15. 15.
    P. Ponka, A. Wilczynska, and H. M. Schulman, Iron utilization in rabbit reticulocytes: A study using succinylacetone as an inhibitor of heme synthesis, Biochim. Biophys. Acta 720: 96 (1982).CrossRefGoogle Scholar
  16. 16.
    P. Ponka and J. Neuwirt, The use of reticulocytes with high non-haem iron pool for studies of regulation of haem synthesis, Brit. J. Haematol. 19: 593 (1970).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • P. Ponka
    • 1
    • 2
  • H. M. Schulman
    • 1
  • J. Edward
    • 3
  1. 1.Lady Davis Institute for Medical ResearchJewish General HospitalMontrealCanada
  2. 2.Departments of PhysiologyMcGill UniversityMontrealCanada
  3. 3.Departments of ChemistryMcGill UniversityMontrealCanada

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