Iminoethers as Carrier Ligands: A Novel trans-Platinum Complex Possessing in Vitro and in Vivo Antitumour Activity

  • Mauro Coluccia
  • Maria A. Mariggiò
  • Angela Boccarelli
  • Francesco Loseto
  • Nicola Cardellicchio
  • Paola Caputo
  • Francesco P. Intini
  • Concetta Pacifico
  • Giovanni Natile

Abstract

The platinum-based anticancer drug cis-[PtCl2(NH3)2] (cis-DDP) is one of the most effective drugs available for the treatment of human tumours,1 whereas its trans isomer (trans-DDP) is inactive.2–6 The clinical efficacy of cis-DDP is, however, limited by tumour cell resistance present either in the onset of treatment (intrinsic) or after an initial response (acquired)7 Cis-DDP resistance appears to be mediated by factors which reduce platinum-DNA adduct formation, e.g. reduced intracellular accumulation, increased inactivation by intracellular thiols, increased repair8 or tolerance of platinum-DNA adducts.9

Keywords

Trans Isomer Platinum Complex Interstrand Crosslinks Planar Ligand Trans Geometry 
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.
    P.J. Loehrer and L.H. Einhorn, Cisplatin, Ann. Inter. Med. 100: 704–713 (1984).CrossRefGoogle Scholar
  2. 2.
    T.A. Connors, M.J. Cleare, and K.R. Harrap, Structure-activity relationships of the antitumour platinum coordination complexes, Cancer Treat. Rep. 63: 1499–1502 (1979).PubMedGoogle Scholar
  3. 3.
    A. Eastman, The formation, isolation, and characterization of DNA adducts produced by anticancer platinum complexes, Pharmacol. Ther. 34: 155–166 (1987).CrossRefPubMedGoogle Scholar
  4. 4.
    J. Reedijk, The mechanism of action of platinum antitumor drugs, Pure Appl. Chem. 59: 181–192(1987).CrossRefGoogle Scholar
  5. 5.
    S.L. Bruhn, J.H. Toney, and S.J. Lippard, Biological processing of DNA modified by platinum anticancer drugs, Prog. Inorg. Chem. 38: 477–516 (1990).CrossRefGoogle Scholar
  6. 6.
    M. Sip, A. Schwartz, F. Vovelle, M. Ptak, and M. Leng, Distortion induced in DNA by cis-platinum interstrand adducts, Biochemistry, 31: 2508–2513 (1992).CrossRefPubMedGoogle Scholar
  7. 7.
    R.F. Ozols and R.C. Young, Chemotherapy of ovarian cancer, Semin. Oncol. 11: 251–263 (1984).PubMedGoogle Scholar
  8. 8.
    W. Zhen, C.J. Link, P.M. O’Connor, E. Reed, R. Parker, S.B. Howell, and V. Bohr, Increased gene-specific repair of cisplatin interstrand crosslinks in cisplatin-resistant human ovarian cancer cell lines, mol. Cell. Biol. 12: 3689–3698 (1992).PubMedGoogle Scholar
  9. 9.
    L.R. Kelland, New platinum antitumor complexes, Crit. Rev. Oncol/Hematol. 15: 191–219 (1993).CrossRefGoogle Scholar
  10. 10.
    K.M. Comess and S.J. Lippard, Molecular aspects of platinum-DNA interactions, in: “Molecular Aspects of Anticancer Drug-DNA Interactions,” Vol. 1, 134–168. S. Neilde and M. Waring, ed., Macmillan Press Ltd., London (1993).Google Scholar
  11. 11.
    A. Eastman, M.M. Jennerwein, and D.L. Nagel, Characterization of bifunctional adducts produced in DNA by trans-diamminedichloroplatinum(II), Chem. Biol. Interact 67:71–80(1988).CrossRefPubMedGoogle Scholar
  12. 12.
    A.P. Pinto and S.J. Lippard, Sequence-dependent termination of in vitro DNA synthesis by cis- and trans-diamminedichloroplatinum(II), Proc. Natl. Acad. Sci. USA, 82: 4616–4619 (1985).CrossRefPubMedGoogle Scholar
  13. 13.
    C.A. Lepre, K.G. Strothkamp, and S.J. Lippard, Synthesis and 1H NMR spectroscopic characterization of trans-[Pt(NH3)2d(AGGCCT) N7-A(1), N7-G(3)], Biochemistry, 26: 5651–5657 (1987).CrossRefPubMedGoogle Scholar
  14. 14.
    V. Brabec and M. Leng, DNA interstrand cross-links of trans-diamminedichloro-platinum(II) are preferentially formed between guanine and complementary cytosine residues, Proc. Natl. Acad. Sci. USA, 90: 5345–5349 (1993).CrossRefPubMedGoogle Scholar
  15. 15.
    N. Farrell, T.T.B. Ha, J.-P. Souchard, F.L. Wimmer, S. Cros, and N.P. Johnsin, Cytostatic trans-platinum(II) complexes. J. Med. Chem. 32: 2240–2241 (1989).CrossRefPubMedGoogle Scholar
  16. 16.
    M. Von Beusichem and N. Farrell, Activation of the trans geometry in platinum antitumor complexes. Synthesis, characterization and biological activity of complexes with planar ligands pyridine, N-methylimidazole, thiazole and quinoline. The crystal and molecular structure of trans-dichloro bis(thiazole) platinum(II). Inorg. Chem. 31: 634–639 (1992).CrossRefGoogle Scholar
  17. 17.
    N. Farrell, L.R. Kelland, J.D. Roberts, and M. Von Beusichem, Activation of the trans geometry in platinum antitumor complexes: a survey of the cytotoxicity of trans compounds containing planar ligands in murine L1210 and human tumor panels and studies on their mechanism of action. Cancer Res. 52: 5065–5072 (1992).PubMedGoogle Scholar
  18. 18.
    M. Coluccia, A. Nassi, F. Loseto, A. Boccarelli, M.A. Mariggiò, D. Giordano, F.P. Intini, P.A. Caputo, and G. Natile, A trans-platinum complex showing higher antitumor activity than the cis congeners. J. Med. Chem. 36: 510–512 (1993).CrossRefPubMedGoogle Scholar
  19. 19.
    L.R. Kelland, C.F.J. Barnard, K.J. Mellish, M. Jones, P.M. Goddard, M. Valenti, A. Bryant, B.A. Murrer, and K.R. Harrap, A novel trans-platinum coordination complex possessing in vitro and in vivo antitumor activity. Cancer Research, 54: 5618–5622 (1994).PubMedGoogle Scholar
  20. 20.
    M. Coluccia, M.A. Mariggiò, A. Boccarelli, F. Loseto, N. Cardellicchio, P.A. Caputo, F.P. Intini, and G. Natile, Unpublished results.Google Scholar
  21. 21.
    R. Cini, P.A. Caputo, F.P. Intini, and G.Natile, Mechanistic and stereochemical investigation of iminoethers formed by alcoholysis of coordinated nitriles: X-ray crystal structure of cis- and trans-[bis(1-imino-1-methoxyethane)dichloroplatinum(II)], Inorg. Chem., in press.Google Scholar
  22. 22.
    M. Coluccia, M. Correale, F.P. Fanizzi, D. Giordano, L. Maresca, M.A. Mariggiò, G. Natile, and M. Tamaro, Mutagenic activity of some platinum complexes: chemical properties and biological activity, Toxicol. Environm. Chem., 8: 1–8 (1984).CrossRefGoogle Scholar
  23. 23.
    A. Eastman and M.A. Barry, Interaction of trans-diammine-dichloroplatinum(II) with DNA: formation of monofunctional adducts and their reaction with glutathione. Biochemistry, 26: 3303–3307 (1987).CrossRefPubMedGoogle Scholar
  24. 24.
    G.L. Cohen, J.A. Ledner, W.R. Bauer, H.M. Ushay, C. Caravana, and S.J. Lippard, Sequence dependent binding of cis-dichlorodiammineplatinum(II) to DNA, J. Am. Chem. Soc. 102: 2487–2488 (1980).CrossRefGoogle Scholar
  25. 25.
    R.B. Ciccarelli, M.J. Solomon, A. Varshavsky, and S.J. Lippard, In vivo effects of cis-and trans-diamminedichloroplatinurn(II) on SV40 chromosomes: differential repair, DNA-protein cross-linking, and inhibition of replication. Biochemistry, 24, 7533–7540(1985).CrossRefPubMedGoogle Scholar
  26. 26.
    S.W. Johnson, R.P. Perez, A.K. Godwin, A.T. Yeung, L.M. Handel, R.F. Ozols, and T.C. Hamilton, Role of platinum-DNA adduct formation and removal in cisplatin resistance in human ovarian cancer cell lines. Biochem. Pharmacol. 47: 687–697 (1994).CrossRefGoogle Scholar
  27. 27.
    M.A. Lemaire, A. Schwartz, A.R. Rahmouni, and M. Leng, Interstrand crosslinks are preferentially formed at the d(GC) sites in the reaction between cis-diamminedichloroplatinum(II) and DNA. Proc. Natl. Acad. Sci. USA, 88: 1982–1985 (1991).CrossRefPubMedGoogle Scholar
  28. 28.
    J. Konopa, J.W. Pawlak, and K. Pawlak, The mode of action of cytotoxic and antitumor 1-nitroacridines. III. In vivo interstrand cross-linking of DNA of mammalian or bacterial cells by 1-nitroacridines. Chem. Biol. Interact. 43: 175–197 (1983).CrossRefPubMedGoogle Scholar
  29. 39.
    A. Skladanowski and J. Konopa, Interstrand DNA crosslinking induced by anthracyclines in tumor cells. Biochemical Pharmacology, 47: 2269–2278 (1994).CrossRefPubMedGoogle Scholar
  30. 30.
    K. Kohn and C.L. Spears, Stabilization of nitrogen-mustard alkylations and interstrand crosslinks in DNA by alkali. Biochim. Biophys. Acta, 145: 734–741 (1967).CrossRefPubMedGoogle Scholar
  31. 31.
    D.C. Gruenert and J.E. Cleaver, Sensitivity of mitomycin C and nitrogen mustard crosslinks to extreme alkaline conditions. Biochem. Biophys. Res. Commun. 123: 549–554 (1984).CrossRefPubMedGoogle Scholar
  32. 32.
    J. Konopa, Adriamycin and Daunomycin induce interstrand crosslinks in HeLa S3 cells. Biochem. Biophys. Res. Commun. 110: 819–826 (1983).CrossRefPubMedGoogle Scholar
  33. 33.
    P.G. Parson, Dependence on treatment time of melphalan resistance and DNA cross-linking in human melanoma cell lines. Cancer Res. 44: 2773–2778 (1984).Google Scholar
  34. 34.
    E.P. Geiduschek, “Reversible” DNA. Proc. Natl. Acad. Sci. USA, 47: 950–955 (1961).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Mauro Coluccia
    • 1
  • Maria A. Mariggiò
    • 1
  • Angela Boccarelli
    • 1
  • Francesco Loseto
    • 1
  • Nicola Cardellicchio
    • 3
  • Paola Caputo
    • 2
  • Francesco P. Intini
    • 2
  • Concetta Pacifico
    • 2
  • Giovanni Natile
    • 2
  1. 1.Dipartimento di Scienze Biomediche e Oncologia UmanaUniversità di BariBariItaly
  2. 2.Dipartimento Farmaco-ChimicoUniversità di BariBariItaly
  3. 3.CNRIstituto Sperimentale TalassograficoTarantoItaly

Personalised recommendations