Ruthenium-Sulfoxide Complexes with a Specific Antimetastatic Activity

  • Enzo Alessio
  • Giovanni Mestroni
  • Gianni Sava
  • Alberta Bergamo
  • Mauro Coluccia
  • Luigi Messori
Part of the NATO ASI Series book series (ASEN2, volume 26)


It is widely known that a square planar platinum(II) complex, cis-PtCl2(NH3)2 (cis- DDP, cisplatin), is a worldwide leading antitumor drug in the chemotherapeutic treatment of human cancer [1]. The complex has high cure rates against testicular carcinomas, and significantly increases the life expectancy of patients with ovarian tumors, head and neck cancers, bladder tumors and osteosarcomas. However, it shows only minor or insufficent activity against a number of malignancies with high social incidence, such as lung carcinomas and adenocarcinomas of the colon and rectum, that are responsible for 30% of cancer mortality. The efficacy of cisplatin is further limited by its rather strong toxic side effects.


Chemical Behavior Ruthenium Complex Tumor Implantation Lung Coloni Spontaneous Lung Metastasis 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Heim, M.E. (1993) Platinum and non-platinum complexes in clinical trials. Current status and new developments, in Keppler, B.K. (ed.). Metal Complexes in Cancer Chemotherapy, VCH, Weinheim, pp. 9–24.Google Scholar
  2. 2.a)
    Gielen, M. (1994) Tin-based antitumor drugs, Metal Based Drugs 1, 213–219. b) Gielen, M. (1995) Tin-based antitumor drugs: new developments, Metal Based Drugs 2, 99-102.CrossRefGoogle Scholar
  3. 3.
    Sadler, P.J. and Rodney, E.S. (1994) The chemistry of gold drugs, Metal Based Drugs 1, 107–144.CrossRefGoogle Scholar
  4. 4.a)
    Köpf-Maier, P. (1993) Antitumor bis(cyclopentadienyl)metal complexes, in Keppler, B.K. (ed.), Metal Complexes in Cancer Chemotherapy, VCH, Weinheim, pp. 259–296. b) Keppler, B.K., Friesen, C., Vongerichten, H. and Vogel, E. (1993) Budotitane, a new tumor-inhibiting titanium compound: preclinical and clinical development, in Keppler, B.K. (ed.), Metal Complexes in Cancer Chemotherapy, VCH, Weinheim, pp. 297-323.Google Scholar
  5. 5.
    Clarke, M.J. (1993) Ruthenium complexes: potential role in anti-cancer pharmaceuticals, in Keppler, B.K. (ed.), Metal Complexes in Cancer Chemotherapy, VCH, Weinheim, pp. 129–156.Google Scholar
  6. 6.
    Keppler, B.K. and Hartmann, M. (1994) New tumor-inhibiting metal complexes. Chemistry and antitumor properties, Metal Based Drugs 1, 145–149.CrossRefGoogle Scholar
  7. 7.
    a) van Vliet, P.M., Toekimin, S.MS., Haasnoot, J.G., Reedijk, X, Novakova, O., Vrana, O. and Brabec, V. (1995) mer-Ru(terpy)Cl3 (terpy = 2, 2′:6′, 2′′-terpyridine) shows biological activity, forms interstrand crosslinks in DNA and binds two guanine derivatives in a trans configuration, Inorg. Chim. Acta 231, 57–64. b) Novakova, O., Kasparova, J., Vrana, O., van Vliet, P. M., Reedijk, J. and Brabec, V. (1995) Correlation between cytotoxicity and DNA binding of ruthenium polypyridyl complexes, Biochemistry 34, 12369-12378.CrossRefGoogle Scholar
  8. 8.a)
    Vilaplana, R.A., Gonzalez-Vilchez, F., Gutierrez-Puebla, E. and Ruiz-Valero, C. (1994) The first antineoplastic Ru(IV) complex: synthesis and structure of [Cl2(l, 2-cyclohexanediaminotetraacetate)Ru]-2H2O, Inorg. Chim. Acta 224, 15–18. b) Vilaplana, R., Romero, M.A., Quiros, M., Salas, J.M. and Gonzalez-Vilchez, F. (1995) Synthesis, structure and antitumor properties of a new l, 2-propylenediaminetetraacetate-ruthenium(III) compound, Metal Based Drugs 2, 211-219.CrossRefGoogle Scholar
  9. 9.
    Coluccia, M., Sava, G., Loseto, F., Nassi, A., Boccarelli, A, Giordano, D., Alessio, E. and Mestroni, G. (1993) Anti-leukaemic action of RuCl2(Me2SO)4 isomers and prevention of brain involvement on P388 leukaemia and on P388/DDP subline, Eur. J. Cancer 29A, 1873–1879.Google Scholar
  10. 10.
    Mestroni, G., Alessio, E., Sava, G., Pacor, S., Coluccia, M. and. Boccarelli, A (1994) Water-soluble ruthenium(III)-dimethyl sulfoxide complexes: chemical behaviour and pharmaceutical properties, Metal Based Drugs 1, 41–63.CrossRefGoogle Scholar
  11. 11.
    Alessio, E., Balducci, G., Lutman, A., Mestroni, G., Calligaris, M. and Attia, W.M. (1993) Synthesis and characterization of two new classes of ruthenium(III)-sulfoxide complexes with nitrogen donor ligands (L): Na[trans-RuCl4(R2 SO)(L)] and mer, cis-RuCl3(R2 SO)(R2SO)(L).-The crystal structure of Na[trans-RuCl4 (Me2 SO)(NH3)] 2Me2SO, Na[trans-RuCl4 (Me2 SO)] H2O, Me2CO (Im = imidazole) and mer, cis-RuCl3(Me2 SO)(Me2SO)(MH3), Inorg. Chim. Acta 203, 205–217.CrossRefGoogle Scholar
  12. 12.
    Sava, G., Pacor, S., Alessio, E., Mestroni, G., Gagliardi, R., Cocchietto, M. and Coluccia, M. (1993) Na[trans-RuCl4(Me2 SO)(Im)] 2Me2SO, Drugs Fut 18, 894–900.Google Scholar
  13. 13.
    Sava, G., Pacor, S., Coluccia, M., Mariggio, M., Cocchietto, M., Alessio, E. and Mestroni, G. (1994) Response of MCa mammary carcinoma to cisplatin and to Na[trans-RuCl4(Me2NSO)(Im)]. Selective inhibition of spontaneous lung metastases by the ruthenium complex, Drug Invest. 8, 150–161.CrossRefGoogle Scholar
  14. 14.
    Chatlas, J., van Eldik, R. and Keppler, B.K. (1995) Spontaneous aquation reactions of a promising tumor inhibitor trans-imidazolium-tetrachllorobis(imidazole)ruthenium(III), trans-HIm[RuCl4(Im)]2 Inorg. Chim. Acta 233, 59–63.CrossRefGoogle Scholar
  15. 15.
    Alessio, E., Sessanta o Santi, A., Faleschini, P., Calligaris, M. and Mestroni, G. (1994) New aspects of rhodium(III)-dimethyl sulfoxide chemistry: synthesis and molecular structure of [NEt4][cis-RhCl4(Me2SO)2] and chemical behaviour in aqueous solution of [RhCln(Me2SO)6−n]3−n (n = 3 or 4) complexes, J. Chem. Soc. Dalton Trans 1849–1855.Google Scholar
  16. 16.
    Messori, L. and Kratz, F. (1994) Transferrin: from inorganic biochemistry to medicine, Metal Based Drugs 1, 161–167.CrossRefGoogle Scholar
  17. 17.
    Kratz, F., Keppler, B.K., Messori, L., Smith, C. and Baker, E.N. (1994) Protein-binding properties of two antitumor Ru(III) complexes to human apotransferrin and apolactoferrin, Metal Based Drugs 1, 169–173.CrossRefGoogle Scholar
  18. 18.
    Messori, L., Kratz, F. and Alessio, E. (1996) The interaction of the antitumor complexes Na[trans-RuCl4(DMSO)(Im)] and Na[trans-RuCl4(DMSO)(Ind)] with apotransferrin: a spectroscopic study, Metal-Based Drugs 3, 1–9.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1997

Authors and Affiliations

  • Enzo Alessio
    • 1
  • Giovanni Mestroni
    • 1
  • Gianni Sava
    • 2
  • Alberta Bergamo
    • 3
  • Mauro Coluccia
    • 4
  • Luigi Messori
    • 5
  1. 1.Department of ChemistryUniversity of TriesteTriesteItaly
  2. 2.Department of Biomedical SciencesUniversity of TriesteTriesteItaly
  3. 3.Fondazione CallerioInstitutes of Biological ResearchTriesteItaly
  4. 4.Department of Biomedical Sciences and Human OncologyUniversity of Bari — PolyclinicBariItaly
  5. 5.Department of ChemistryUniversity of FlorenceFlorenceItaly

Personalised recommendations