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Pharmaceutisch Weekblad

, Volume 7, Issue 5, pp 173–180 | Cite as

Cisplatin: Synthesis, antitumour activity and mechanism of action

  • J. Reedijk
  • P. H. M. Lohman
Review Articles

Abstract

A review is presented on the successful antitumour drugcis-diamminedichloroplatinum(II), better known as cisplatin. Special attention is given to the synthesis of the compound and related derivatives, and to the nature of the hydrolysis products in blood and in the cell. In the second part of the review the mechanism of action is discussed. Binding to DNA and in particular the formation of intrastrand cross-links between adjacent guanines, to which the Pt(NH3)22+ ion is chelated at the N7 atoms, seems to be a very important event. However, at the moment it is not yet known which DNA lesion is responsible for the killing of the tumour cells.

Keywords

Public Health Tumour Cell Internal Medicine Guanine Hydrolysis Product 
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.
    Reedijk J. Nomenclature for platinum antitumour compounds. In: Hacker MP, Douple EB, Krakoff M, eds. Platinum coordination complexes in cancer chemotherapy. Boston: M. Nijhoff, 1984:3–8.Google Scholar
  2. 2.
    Rosenberg B, Van Camp L, Krigas T. Inhibition of cell division inEscherichia coli by electrolysis products from a platinum electrode. Nature 1965;205:698–9.PubMedGoogle Scholar
  3. 3.
    Rosenberg B, Van Camp L, Grimley EB, Thomson AJ. The inhibition of growth or cell division inEscherichia coli by different ionic species of platinum(IV) complexes. J Biol Chem 1967;242:1347–52.PubMedGoogle Scholar
  4. 4.
    Rosenberg B, Van Camp L, Trosko JE, Mansour VH. Platinum compounds: a new class of potent antitumour agents. Nature 1969;222:385–6.PubMedGoogle Scholar
  5. 5.
    Roberts JJ, Thomson AJ. The mechanism of action of antitumour platinum compounds. Progr Nucleic Acid Res Mol Biol 1979;22:71–133.Google Scholar
  6. 6.
    Wiltshaw E. Cisplatin in the treatment of cancer. Plat Met Rev 1979;23:90–8.Google Scholar
  7. 7.
    Marzilli LG, Eichorn GL. Metal-ions in genetic information transfer. New York: Elsevier/North Holland, 1984.Google Scholar
  8. 8.
    Van Kralingen CG. Antitumor Platinum Compounds: Synthesis, structure and biological activity. Delft: Delft University of Technology, 1979. Dissertation.Google Scholar
  9. 9.
    Marcelis ATM. Interaction of antitumor platinum compounds with nucleic acid fragments. Leiden: State University of Leiden, 1982. Dissertation.Google Scholar
  10. 10.
    Marcelis ATM, Reedijk J. Binding of platinum compounds to nucleic acids, in relation to the antitumor activity ofcis-diamminedichloroplatinum (II) and derivatives. Recl Trav Chim Pays Bas 1983;102:121–9.Google Scholar
  11. 11.
    Martin RB. Hydrolytic equilibria and N7 versus N1 binding in purine nucleosides ofcis-diamminedichloro-platinum(II). In: Lippard SJ, ed. Platinum, gold and other metal chemotherapeutic agents: chemistry and biochemistry. Washington American Chemical Society, 1983:231–44. (ACS Symposium Series. Vol. 209).Google Scholar
  12. 12.
    Lippard SJ. New chemistry of an old molecule:cis-Pt(NH3)2Cl2. Science 1982;218:1075–82.PubMedGoogle Scholar
  13. 13.
    Pinto A, Kippard SJ. Binding of the antitumor drugcis-diamminedichloroplatinum(II) (cisplatin) to DNA. Biochim Biophys Acta 1985;780:167–80.PubMedGoogle Scholar
  14. 14.
    Prestayko AW, Crooke ST, Carter SK, eds. Cisplatin, current status and new developments. New York: Academic Press, 1980.Google Scholar
  15. 15.
    Rosenberg B. Some biological effects of platinum compounds. Plat Met Rev 1971;15:42–4.Google Scholar
  16. 16.
    Reslova S. The induction of lysogenic strains ofEscherichia coli bycis-dichlorodiammineplatinum(II). Chem Biol Interact 1972;4:66–70.Google Scholar
  17. 17.
    Harder HC, Smith RG, Leroy AF. Template primer inactivation bycis- andtrans-dichlorodiammine platinum for human DNA polymerase α, β, and Rauscher Murine Leukemia Virus reverse transcriptase, as a mechanism of cytotoxicity. Cancer Res 1976;36:3821–9.PubMedGoogle Scholar
  18. 18.
    Gellert RW, Bau R. X-ray structural studies of metal-nucleoside and metal-nucleotide complexes. In: Sigel H, ed. Metal ions in biological systems. Vol. 8. New York: Marcel Dekker, 1979:1.Google Scholar
  19. 19.
    Brouwer J, VandePutte P, Fichtinger-Schepman AMJ, Reedijk J. Base-pair substitution hotspots in GAG and GCC nucleotide sequences inEscherichia coli K-12 induced bycis-diamminedichloroplatinum(II). Proc Natl Acad Sci USA 1981;78:7010–4.PubMedGoogle Scholar
  20. 20.
    Fichtinger-Schepman AMJ, Lohman PHM, Reedijk J. Detection and quantification of adducts formed upon interaction of diamminedichloroplatinum(II) with DNA, by anion-exchange chromatography after enzymatic degradation. Nucl Acid Res 1982;10:5345–56.Google Scholar
  21. 21.
    Fichtinger-Schepman AMJ, Van der Veer JL, Den Hartog JHJ, Lohman PHM, Reedijk J. Adducts of the antitumor drugcis-diamminedichloroplatinum(II) with DNA: formation, identification and quantitation. Biochemistry 1985;24:707–13.CrossRefPubMedGoogle Scholar
  22. 22.
    Rahn RO. Chromatographic analysis of the adducts formed in DNA complexed withcis-diamminedi-chloroplatinum (II). J Inorg Biochem 1984;21:311–21.CrossRefPubMedGoogle Scholar
  23. 23.
    Plooij ACM. Effects of cisplatin and related cis- and transplatinum compounds on cultured mammalian cells: genotoxic properties and their molecular background. Leiden: State University of Leiden, 1984. Dissertation.Google Scholar
  24. 24.
    Chottard JC, Girault JP, Chottard G, Lallemand JY, Mansuy D. Interaction ofcis-[Pt(NH3)2(H2O)2](NO3)2 with ribose dinucleoside monophosphates. J Am Chem Soc 1980;102:5565–72.CrossRefGoogle Scholar
  25. 25.
    Den Hartog JHJ, Altona C, Chottard JC, et al. Conformational analysis of the adductcis-Pt(NH3)2d(GpG) in aqueous solution. A high field (500-300 MHz) nuclear magnetic resonance investigation. Nucl Acid Res 1982;10:4715–30.Google Scholar
  26. 26.
    Den Hartog JHJ. Cisplatin induced distortions in DNA. Leiden: State University of Leiden, 1985. Dissertation.Google Scholar
  27. 27.
    Marcelis ATM, Den Hartog JHJ, Reedijk J. Intrastrand cross-linking of the guanines of the deoxytrinucleotide d(G-C-G) viacis-Pt(NH3)2Cl2. J Am Chem Soc 1982;104:2664–5.CrossRefGoogle Scholar
  28. 28.
    Marcelis ATM, Canters GW, Reedijk J. Chelation ofcis-Pt(NH3)2Cl2 by the deoxynucleotide d(C-C-G-G). Recl Trav Chim Pays-Bas 1981;100:391–2.Google Scholar
  29. 29.
    Tran-Dinh S, Neumann JM, Girault JP, Chottard JC, Igolen J, Huynh-Dinh T. Conformation of d(ATGG)-cisPt(NH3)2 in aqueous solution by proton magnetic resonance spectroscopy. Inorg Chim Acta 1983;79:253–4.CrossRefGoogle Scholar
  30. 30.
    Girault JP, Chottard JC, Guittet ER, Lallemand JY, Huynh-Dinh T, Igolen J. Specific platinum chelation by the guanines of the deoxyhexanucleotide d(T-G-G-C-C-A) upon reaction withcis-[Pt(NH3)2(H2O)2](NO3)2. Biochem Biophys Res Commun 1983;109:1157–63.Google Scholar
  31. 31.
    Caradonna JP, Lippard SJ, Gait MJ, Singh M. The antitumor drugcis-[Pt(NH3)2Cl2] forms an intrastrand d(GpG) cross-link upon reaction with [d(ApGpGpCpCpT)]2. J Am Chem Soc 1982;104:5793–5.CrossRefGoogle Scholar
  32. 32.
    Den Hartog JHJ, Altona C, Van Boom JH, Van der Marel GA, Haasnoot CAG, Reedijk J.cis-Diammine-dichloroplatinum(II) induced distortion in a doublehelical DNA fragment. J Am Chem Soc 1984;106:1528–30.Google Scholar
  33. 33.
    Marzilli LG, Reily MD, Heyl BL, McMurray CT, Wilson WD. Evidence for similar structural changes on binding of platinum anti-tumor agents to DNA and nucleosomes. FEBS Lett 1984;176:389–92.CrossRefPubMedGoogle Scholar
  34. 34.
    Den Hartog JHJ, Altona C, Van Boom JH, Reedijk J. A phosphorus NMR study of the reaction products ofcis-diamminedichloroplatinum(II) with a double helical oligonucleotide and with DNA. FEBS Lett 1984;176:393–7.Google Scholar

Copyright information

© Bohn, Scheltema & Holkema 1985

Authors and Affiliations

  • J. Reedijk
    • 1
  • P. H. M. Lohman
    • 2
  1. 1.Department of Chemistry, Gorlaeus LaboratoriesState University of LeidenRA LeidenThe Netherlands
  2. 2.Medical Biological Laboratory TNOAA RijswijkThe Netherlands

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