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Phenols and Polyphenols as Antioxidants and Anticancer Agents

  • H. L. Elford
  • B. Van’t Riet
Chapter
Part of the Developments in Oncology book series (DION, volume 67)

Abstract

In order to replicate, a mammalian cell must replicate its genetic material which involves the synthesis of DNA. The reductive conversion of ribonucleotides to deoxynucleotides, catalyzed by the enzyme ribonucleotide reductase, is a rate limiting step in the DNA biosynthetic pathway (1). The endogenous pools of deoxynucleotides are not sufficient to support de novo DNA synthesis. Therefore, this key step in DNA synthesis represents a prime target for the development of an anticancer compound. Mammalian ribonucleotide reductase consists of two non-identical protein subunits. The larger subunit acts as a regulatory subunit since it contains the allosteric effectors (nucleotides) binding domains. The small subunits contain a pair of ferric ions and are able to generate a tyrosyl free radical which play a vital role in the reductive reaction (2). The reducing equivalents is supplied by either of two small molecular weight sulfhydryl proteins thioredoxin or glutaredoxin (1).

Keywords

Hydroxamic Acid Ribonucleotide Reductase Allosteric Effector Inhibit Ribonucleotide Reductase Exhibit Antitumor Activity 
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.

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References

  1. 1.
    Reichard, P. Ann. Rev. Biochem. 57:349–374, 1988.PubMedCrossRefGoogle Scholar
  2. 2.
    Graslund, A., Ehrenberg, A. and Thelander, L. J. Biol. Chem. 257:5711–5719, 1982.Google Scholar
  3. 3.
    Elford, H.L. and Van’t Riet, B. Pharmac. Ther. 29:239–254, 1985.CrossRefGoogle Scholar
  4. 4.
    Elford, H.L., Wampler, G.L. and Van’t Riet, B. Cancer Res. 39:844–851, 1979.PubMedGoogle Scholar
  5. 5.
    Elford, H.L, Van’t Riet, B., Wampler, G.L, Lin, A.L. and Elford, R.M. Adv. Enz. Reg. 19:151–168, 1981.CrossRefGoogle Scholar
  6. 6.
    Elford, H.L. and Van’t Riet, B. In: International Encyclopedia of Pharmacology and Therapeutics (Eds. J.G. Cory and A.H. Cory), Pergamon Press, Elmsford, N.Y., 1989, pp. 217–233.Google Scholar
  7. 7.
    Yamafuji, K. and Murakami, H. Enzymologia 35:139–153, 1968.PubMedGoogle Scholar
  8. 8.
    Angeletti, P.U. and Levi-Montalcini, R. Cancer Res. 30:2863–2869, 1970.PubMedGoogle Scholar
  9. 9.
    Chelmicka-Szorc, E. and Arnason, B.G.W. Cancer Res. 36:2382–2384, 1976.PubMedGoogle Scholar
  10. 10.
    Wick, M.M. Cancer Treat. Rep. 63:991–997, 1979.PubMedGoogle Scholar
  11. 11.
    Driscoll, J.S. J. Pharm. Sci. 68:1519–1521, 1979.CrossRefGoogle Scholar
  12. 12.
    Vogel, F.S., Kemper, L.A.K., Boekelheide, K., Graham, D.G. and Jeffs, P.W. Cancer Res. 39:1490–1493, 1979.PubMedGoogle Scholar
  13. 13.
    Gianni, L., Corden, B.J. and Myers, C.E. In: Review in Biochemical Toxicology (Eds. Hodgson, et al.), Elsevier, N.Y., 1983, pp. 1–82.Google Scholar
  14. 14.
    Elford, H.L., Van’t Riet, B., Wampler, G.L., Searle, A. and Willson, R.L. Proc. Am. Ass. Cancer Res. 24:326, 1983.Google Scholar
  15. 15.
    Snyder, R.D. Cell Biol. Toxicol. 1:49–57, 1984.CrossRefGoogle Scholar
  16. 16.
    Piver, M.S., Khalil, M. and Emrich, L.J. J. Surg. Oncol. 42:120–125, 1989.CrossRefGoogle Scholar
  17. 17.
    Stehman, F.B., Bundy, B.N., Keys, H., Currie, J.L., Mortel, R. and Creasman, W.T. Am. J. Obstet. Gynecol. 159:87–94, 1988.PubMedGoogle Scholar
  18. 18.
    Russell, K.J., Elford, H.L. and Brown, J.M. Submitted for publication.Google Scholar
  19. 19.
    Wattenberg, L.W. Cancer Res. 45:1–8, 1985.PubMedCrossRefGoogle Scholar
  20. 20.
    Kozumbo, W., Seed, J.L. and Kensler, T.W. Cancer Res. 43:2555–2559, 1983.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • H. L. Elford
    • 1
  • B. Van’t Riet
    • 1
  1. 1.Molecules for Health Inc.RichmondUSA

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