The Involvement of Free Radicals in the Metabolism of Drugs

  • V. Malatesta
Part of the NATO ASI Series book series (ASIC, volume 260)


The cytotoxycity of the anthracycline antitumour drugs results from multiple biochemical alterations of the cellular organization at several levels. The expression of the cytotoxic effects is subsequent to the activation of the drug through: reduction, metalion complexation and irradiation. A correlation between the cardiotoxicity, the main side-effect displayed by these drugs, the reductive deglycosidation and the metal-ion catalyzed side-chain degradation is proposed.


Singlet Oxygen Platelet Membrane Quench Rate Constant Photosensitize Action Singlet Oxygen Quantum Yield 
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  1. 1.
    Mimnaugh, E. G., Trush, M. A., Bhatnagar, M. and Gram, T.E.: 1981, Toxicol Appl.Pharmacol. 61, pp. 313–325.CrossRefGoogle Scholar
  2. 2.
    Mailer, K. and Petering, D. H.: 1976, Biochem. Pharmacol. 25, pp. 2085–2089.CrossRefGoogle Scholar
  3. 3.
    Goormaghtigh, E., Chatelain, P., Caspers, J. and Ruysschaert, J. M.: 1980, Biochem. Pharmacol. 29, pp. 3003–3010.CrossRefGoogle Scholar
  4. 4.
    Malatesta, V. and Andreoni, A.: 1988, J. Photochem. Photobiol. in pressGoogle Scholar
  5. 5.
    Chaires, J. B., Dattagupta, A. and Crothers, D. M.: 1985, Biochemistry, 24, pp. 260–267.CrossRefGoogle Scholar
  6. 6.
    Malatesta, V. and Andreoni, A.: 1988, Photochem. Photobiol. in pressGoogle Scholar
  7. 7.
    Sinha, B. K., Trush, M. A., Kennedy, K. A. and Mimnaugh, E.G.: 1984, Cancer Res. 44, pp.2892–2896.Google Scholar
  8. 8.
    Someya, A. and Tanaka, N.: 1979, J. Antibiot. 32, pp. 839–845.Google Scholar
  9. 9.
    Mimnaugh, E. G., Trush, M. A., Bhatnagar, M. and Garm, T. E.: 1984, Biochem. Pharmacol. 34, pp. 847–856.CrossRefGoogle Scholar
  10. 10.
    Kharasch, E. D. and Novak, R. F.: 1983, J. Pharmacol. Exp. Ther. 226, pp. 500–506.Google Scholar
  11. 11.
    Babson, J. R., Abell, N. S. and Reed, D. J.: 1981, Biochem. Pharmacol. 30, pp. 2299–2304.CrossRefGoogle Scholar
  12. 12.
    Mimnaugh, E. G., Kennedy, K. A., Trush, M. A. and Sinha, B. K.: 1985, Cancer Res. 45, pp. 3296–3304.Google Scholar
  13. 13.
    Malatesta, V., Penco, S., Sacchi, N., Valentini, L., Vigevani, A., and Arcamone, F.: 1984, Can. J. Chem. 62, pp. 2845–2850.CrossRefGoogle Scholar
  14. 14.
    Pan, S., Pedersen, L. and Bachur, N. R.: 1981, Molec. Pharmacol. 19, pp. 184–186.Google Scholar
  15. 15.
    Sinha, B. K. and Gregory, J. L.: 1981, Biochem. Pharmacol. 130, pp. 2626–2631.CrossRefGoogle Scholar
  16. 16.
    Penco, S., Malatesta, V., Barchielli, G., Sacchi, N., Bordoni, T., Bellini, O. and Arcamone, F.: Molec. Pharmacol. submittedGoogle Scholar
  17. 17.
    Doroshow, J. H. and Davies, J. A.: 1986, J. Biol. Chem. 261, pp. 3068–3074.Google Scholar
  18. 18.
    Malatesta, V.: 1988, Med. Biol. Envir. 16, pp. 77–82.Google Scholar
  19. 19.
    May, P. M, Williams, G. N. and Williams, D. R.: 1980, Eur. J. Cancer 16, pp. 1275–1276.Google Scholar
  20. 20.
    Beraldo, H., Garnier-Suillerot, A. and Tosi, L.: 1983, Inorg. Chem. 22, pp. 4117–4124.CrossRefGoogle Scholar
  21. 21.
    Gianni, L., Viganö, L., Lanzi, C., Niggeler, M. and Malatesta, V.: 1988, Cancer Res. in pressGoogle Scholar
  22. 22.
    Malatesta, V., Tosi, C. and Fusco, R.; 1986, Chem. Phys. Lett. 128, pp. 565–568.CrossRefGoogle Scholar
  23. 23.
    Thomas, G. E. and Aust, S. D.: 1986, Archiv. Biochem. Biophys. 248, pp. 684–689.CrossRefGoogle Scholar
  24. 24.
    Halliwell, B., Gutteridge, J. M. and Blake, D.: 1985, Philos. Trans. R. SOC. London, Series B 311, pp.659–671.CrossRefGoogle Scholar
  25. 25.
    Phillips, D. R. and Carlyle, G. A.: 1981, Biochem. Pharmacol. 30, pp. 2021–2024.CrossRefGoogle Scholar
  26. 26.
    Malatesta, V., Morazzoni, F., Gervasini, A. and Arcamone, F.: 1985, Anti Cancer Drug Design 1, pp. 53–57.Google Scholar
  27. 27.
    Morazzoni, F., Gervasini, A. and Malatesta, V.: 1987, Inorg. Chim. Acta 136, pp. 111–115.CrossRefGoogle Scholar
  28. 28.
    Malatesta, V., Gervasini, A. and Moarazzoni, F.: 1987, Inorg. Chim. Acta 136, pp. 81–85.CrossRefGoogle Scholar
  29. 29.
    Malatesta, V., Morazzoni, F., Pellicciari-Bollini, L. and Scotti, R.: 1987, J. Chem. Soc. Faraday Trans. I 83, pp. 3669–3673.CrossRefGoogle Scholar
  30. 30.
    Malatesta, V., Morazzoni, F., Piccinini, F. and Monti, E.: in preparationGoogle Scholar
  31. 31.
    Malatesta, V. and Sacchi, N.: unpublished resultsGoogle Scholar
  32. 32.
    Li, A. S. W. and Chignell, F.: 1987, Photochem. Photobiol. 45, pp. 565–570.CrossRefGoogle Scholar
  33. 33.
    Reilly, J. J., Neifeld, J. P. and Rosenberg, S. A.: 1977, Cancer 40, pp. 2053–2056.CrossRefGoogle Scholar
  34. 34.
    Sanfilippo, A. G., Schioppacassi, G., Movillo, E. and Ghione, M.: 1968, G. Microbiol. 16, pp. 49–54.Google Scholar
  35. 35.
    Verini, M. A., Casazza, A. M, Fioretti, A., Rodenghi, F. and Ghione, M.: 1968, G. Microbiol. 16, pp. 55–64.Google Scholar
  36. 36.
    Gray, P. J., Phillips, D. R. and Wedd, A.G.: 1982, Photochem. Photobiol. 36, pp. 49–57.CrossRefGoogle Scholar
  37. 37.
    Carmichael, A. J. and Riesz, P.: 1985, Archiv. Biochem. Biophys. 236, pp. 433–444.CrossRefGoogle Scholar
  38. 38.
    Andreoni, A., Land, T., Malatesta, V., McLean, A. and Truscott, T. G.: J. Chem. Soc. submittedGoogle Scholar
  39. 39.
    Manitto, P., Speranza, G. and Malatesta, V.: J. Am. Chem. Soc. submittedGoogle Scholar
  40. 40.
    Andreoni, A., Colasanti, A., Kisslinger, A. M. and Malatesta, V. in preparationGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • V. Malatesta
    • 1
  1. 1.R. & D. Farmitalia-Carlo ErbaMilanoItaly

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