Advertisement

Platinum (II) Polyamines: Relationship of Chain Length to Biological Activity

  • Deborah W. Siegmann
  • Charles E. CarraherJr.
  • Dora Brenner

Abstract

Platinum (II) polyamines, which are polymeric analogues of the cancer drug cis-DDP, were synthesized and tested for biological activity. It was hoped that such compounds would retain the anti-tumor activity of cis-DDP but produce fewer toxic side effects. The results obtained from cell culture show that several of the polymers can kill cells and/or inhibit cell growth of growing cells but do not affect quiescent cells. The level of activity displayed by these polymers is equal to or greater than that of cis-DDP. Since some polymers are biologically active while others are not, several factors which could influence activity were considered. One such factor is the size of the polymers. The polymer chain length could determine how easily the polymer enters the cell and how well it binds to and damages cellular macromolecules. The size of the various platinum polyamines was measured using light scattering photometry and Sephacryl column chromatography. It was found that the polymers have a wide range of molecular weights. Furthermore, in some cases, two molecular weight classes exist within one polymer preparation, suggesting two different modes of polymer synthesis. However, no correlation was seen between the size of a polymer and its biological activity. Thus, molecular weight does not appear to be an important factor in determining the biological effects of these platinum polyamines.

Keywords

Polymer Concentration Elution Profile Elution Volume Quiescent Cell Toxic Side Effect 
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.
    B. Rosenberg, L. Van Camp & T. Krigas, Nature, Lond., 205, 698 (1965).CrossRefGoogle Scholar
  2. 2.
    B. Rosenberg, L. Van Camp, E. G. Grimley & A. J. Thomson, J. Biol. Chem., 242, 1347 (1967).Google Scholar
  3. 3.
    S. Resolva, Chem.-Biol. Interact., 4, 66 (1971).CrossRefGoogle Scholar
  4. 4.
    L. Kutinova, V. Vonka & J. Drobnik, Neoplasma, 19, 453 (1972).Google Scholar
  5. 5.
    D. J. Beck & R. P. Brubaker, Mutat. Res., 27, 181 (1975).CrossRefGoogle Scholar
  6. 6.
    W. R. Leopold, E. C. Miller & J. A. Miller, Cancer Res., 39, 913 (1979).Google Scholar
  7. 7.
    B. Rosenberg, L. Van Camp, J. E. Trosko & V. H. Mansour, Nature, London., 222, 385 (1969).CrossRefGoogle Scholar
  8. 8.
    A. W. Prestayko, J. C. D’Aoust, B. F. Issell & S. T. Crooke, Cancer Treat. Rev., 6, 17 (1979).CrossRefGoogle Scholar
  9. 9.
    E. Wiltshaw & B. Carr in: “Recent Results in Cancer Research: Platinum Coordination Complexes in Cancer Therapy,” T. A. Connors & J. J. Roberts, Eds., Springer-Verlag, New York, 1974, p. 178.CrossRefGoogle Scholar
  10. 10.
    T. F. Reynolds, D. Vugrin, E. Cvitkovic, E. Cheng, D. W. Braun, M. A. Ohehir, M. E. Dukeman, W. E. Whitmore & R. B. Golby, Cancer, 48, 888 (1981).CrossRefGoogle Scholar
  11. 11.
    J. J. Roberts & A. J. Thomson, Prog. Nucl. Acid Res. Mol. Biol., 22, 71 (1979).CrossRefGoogle Scholar
  12. 12.
    J. J. Roberts & M. P. Pera in: “Molecular Aspects of Anti-Cancer Drug Action,” S. Neidle & M. J. Waring, Eds., MacMillan Press, London, 1983, p. 183.Google Scholar
  13. 13.
    D. B. Brown, A. R. Khokhar, M. P. Macker, J. J. McCormack & R. A. Newman in: “Platinum, Gold, and Other Metal Chemotherapeutic Agents,” S. J. Lippard, Ed., American Chemical Society, Washington, DC, 1983, p. 265.CrossRefGoogle Scholar
  14. 14.
    M. C. Lim & R. B. Martin, J. Inorg. Nucl. Chem., 38, 1911 (1976).CrossRefGoogle Scholar
  15. 15.
    P. Horacek & J. Drobnik, Biochem. Biophys. Acta., 254, 341 (1971).CrossRefGoogle Scholar
  16. 16.
    S. Mansy, B. Rosenberg & A. J. Thomson, J. Am. Chem. Soc., 95, 1633 (1973).CrossRefGoogle Scholar
  17. 17.
    J. J. Roberts & J. M. Pascoe, Nature, Lond., 235, 282 (1972).CrossRefGoogle Scholar
  18. 18.
    M. M. Millard, J-P. Macquet & T. Theophanides, Biochim. Biophys. Acta., 402, 166 (1975).CrossRefGoogle Scholar
  19. 19.
    H. N. A. Fraval & J. J. Roberts, Chem.-Biol. Interact., 23, 99 (1978).CrossRefGoogle Scholar
  20. 20.
    L. A. Zwelling, T. Anderson & K. W. Kohn, Cancer Res., 39, 365 (1979).Google Scholar
  21. 21.
    H. N. A. Fravel & J. J. Roberts, Cancer Res., 39, 1793 (1979).Google Scholar
  22. 22.
    H. C. Harder & B. Rosenberg, Int. J. Cancer, 6, 207 (1970).CrossRefGoogle Scholar
  23. 23.
    J. M. Pascoe & J. J. Roberts, Biochem. Pharmac, 23, 1359 (1974).CrossRefGoogle Scholar
  24. 24.
    M. Zak, J. Drobnik & Z. Rezny, Cancer Res., 32, 565 (1972).Google Scholar
  25. 25.
    J. A. Gottlieb & B. Drewinko, Cancer Chemother. Rep., 59, 621 (1975).Google Scholar
  26. 26.
    A. M. Guarino, D. S. Miller, S. T. Arnold, J. B. Pritchard, R. D. Davis, M. A. Urbanek, T. L. Miller & C. L. Litterst, Cancer Treat. Rep., Proc. NCI Conf. on cis-Platinum and Testicular Cancer, 63, 1475, (1979).Google Scholar
  27. 27.
    M. Cleare & P. Hoeschele, Platinum Metals Rev., 17, 2 (1973).Google Scholar
  28. 28.
    N. Farrell in: “Platinum, Gold, and Other Metal Chemotherapeutic Agents,” S. Lippard, Ed., American Chemical Society, Washington, DC, 1983, p. 279.CrossRefGoogle Scholar
  29. 29.
    J. Freise & P. Magerstedt in: “Liposomes Drug Carriers Symposium,” K. H. Schmidt, Ed., 1986, p. 182.Google Scholar
  30. 30.
    B. Hecquet, G. Depadt, C. Fourier & J. Meynadier, Anticancer Res., 6, 659 (1986).Google Scholar
  31. 31.
    S. Volles, R. M. Roat, M. F. Satori & C. L. Washburne in: “Biological Activities of Polymers,” C. E. Carraher & C. G. Gebelein, Eds., American Chemical Society, Washington, DC, 1982, p. 233.CrossRefGoogle Scholar
  32. 32.
    B. Schechter, R. Pauzner, M. Wilchek & R. Arnon, Cancer Biochem. Biophys., 8, 289 (1986).Google Scholar
  33. 33.
    C. Carraher, J. Schroeder, D. Giron & W. Scott, J. Macromol. Sci-Chem., A15 (4), 625, (1981).Google Scholar
  34. 34.
    C. E. Carraher, D. J. Giron, I. Lopez, D. R. Cerutis & W. J. Scott, Org. Coatings Plast. Chem., 44, 120 (1981).Google Scholar
  35. 35.
    J. Davidson, D. Faber & R. Fischer, Cancer Chemother. Rep., 59, 287 (1975).Google Scholar
  36. 36.
    C. Litterst, T. Gram, R. Dedrick, A. Leroy & A. Guarino, Cancer Res., 36, 2340 (1966).Google Scholar
  37. 37.
    C. E. Carraher, W. J. Scott & D. J. Giron in: “Bioactive Polymeric Systems,” C. G. Gebelein & C. E. Carraher, Eds., Plenum Press, New York, 1985, p. 587.CrossRefGoogle Scholar
  38. 38.
    C. J. L. Lock, J. Bradford, R. Faggiani, R. A. Speranzini, G. Turner & M. Zvagulis, J. Clin. Hemat. Oncol., 7, 63 (1977).Google Scholar
  39. 39.
    A. Allcock, Science, 193, 1214 (1976).CrossRefGoogle Scholar
  40. 40.
    C. Carraher, T. Manek, D. Giron, D. R. Cerutis & M. Trombley, Polym. Prepr., 23, 77 (1982).CrossRefGoogle Scholar
  41. 41.
    A. Allcock in: “Organometallic Polymers,” C. Carraher, J. Sheats & C. Pittman, Eds., Academic Press, New York, 1978. Chap. 28.Google Scholar
  42. 42.
    C. E. Carraher, W. J. Scott, I. Lopez, D. R. Cerutis & R. Manek in: “Biological Activities of Polymers,” C. E. Carraher & C. G. Gebelein, Eds., American Chemical Society, Washington, DC, 1982, p. 221.CrossRefGoogle Scholar
  43. 43.
    T. A. Connors, M. Jones, W. C. J. Ross, P. D. Braddock, A. R. Khokhar & M. L. Tobe, Chem.-Biol. Interact., 5, 415 (1972).CrossRefGoogle Scholar
  44. 44.
    P. D. Braddock, T. A. Connors, M. Jones, A. R. Khokhar, D. H. Melzack & M. L. Tobe, Chem.-Biol. Interact., 11, 145 (1975).CrossRefGoogle Scholar
  45. 45.
    H. Into, J. Fugita & K. Sato, Bull. Chem. Soc. Japan, 40, 1584 (1967).Google Scholar
  46. 46.
    A. A, Grinberg, M. Serator & M. L. Gellfman, Russian J. Inorg. Chem., 13, 1695 (1968).Google Scholar
  47. 47.
    F. A. Cotton & G. Wilkenson, “Advanced Inorganic Chemistry,” Interscience, New York, 1978.Google Scholar
  48. 48.
    J. E. Huheey, “Inorganic Chemistry,” 3rd Ed., Harper and Row, New York, 1983.Google Scholar
  49. 49.
    A. J. Thomson, I. A. G. Roos & R. D. Graham, J. Clin. Hemat. Oncol., 7, 242 (1977).Google Scholar
  50. 50.
    H. J. Wallace & D. J. Higby, Recent Results Cancer Res., 48, 167 (1974).CrossRefGoogle Scholar
  51. 51.
    D. W. Siegmann, C. E. Carraher & A. Friend, J. Polym. Mater., 4, 19 (1987).Google Scholar
  52. 52.
    D. W. Siegmann & C. E. Carraher, J. Polym. Mater., 4, 29 (1987).Google Scholar
  53. 53.
    H. N. A. Fravel, C. J. Rawlings & J. J. Roberts, Mutat. Res., 51, 121 (1978).CrossRefGoogle Scholar
  54. 54.
    M. F. Pera, C. J. Rawlings & J. J. Roberts, Chem.-Biol. Interact., 37, 245 (1981).CrossRefGoogle Scholar
  55. 55.
    H. Bourne & E. Rozengurt, Proc. Nat. Acad. Sci., USA, 73, 4555 (1976).CrossRefGoogle Scholar
  56. 56.
    S. Futterman, J. Biol. Chem., 228, 1031 (1957).Google Scholar
  57. 57.
    R. B. Livingston & S. K. Carter in: “Single Agents in Cancer Chemotherapy,” Plenum Press, London, 1970, p. 131.CrossRefGoogle Scholar
  58. 58.
    N. P. Johnson, J. D. Hoeschele, R. O. Rahn, J. P. O’Neill & A. W. Hsie, Cancer Res., 40, 1463 (1980).Google Scholar
  59. 59.
    R. Dagani, Science, 16, 20 (1985).Google Scholar
  60. 60.
    P. J. Debye, J. Phys. Pol. Chem., 51, 1 (1947)CrossRefGoogle Scholar
  61. 61.
    R. Seymour & C. E. Carraher, “Polymer Chemistry: An Introduction,” Dekker, New York, 1982.Google Scholar
  62. 62.
    J. R. Whitaker, Anal. Chem., 35, 1950 (1963).CrossRefGoogle Scholar
  63. 63.
    P. G. Squire, Arch. Biochem. Biophys., 107, 471 (1967).CrossRefGoogle Scholar
  64. 64.
    D. T. Sawyer, W. R. Heineman & J. M. Beebe in: “Chemistry Experiments for Instrumental Methods,” John Wiley and Sons, New York, 1984, p. 361.Google Scholar
  65. 65.
    D. W. Siegmann, D. Brenner, C. E. Carraher & R. E. Strother, Polymeric Materials Science and Engineering, in press.Google Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Deborah W. Siegmann
    • 1
  • Charles E. CarraherJr.
    • 1
  • Dora Brenner
    • 1
  1. 1.Department of ChemistryFlorida Atlantic UniversityBoca RatonUSA

Personalised recommendations