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Organometallic titanium, vanadium, niobium, molybdenum and rhenium complexes — early transition metal antitumour drugs

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Metal Compounds in Cancer Therapy

Abstract

Titanocene dichloride, bis(cyclopentadienyl)dichlorotitanium(IV), [(C5H5)2TiCl2] (Figure 6.1) is the main representative of the early transition metal antitumour agents to show antitumour activity against numerous experimental animal and human carcinomas (Köpf and Köpf-Maier, 1979; Köpf-Maier Hesse and Köpf, 1980; Köpf-Maier, Leitner and Köpf, 1980; Köpf-Maier and Köpf, 1988) and entered phase I clinical studies in December 1991. It is one of the first non-platinum antitumour agents to be detected after the discovery of the tumour-inhibiting properties of cis-diamminedichloroplatinum(II) (cisplatin, Figure 6.1) in 1969 (Rosenberg et al., 1969; Rosenberg, 1973). As a chemical compound, titanocene dichloride was described by Wilkinson and Birmingham in 1954 and is today an important organometallic compound used as ‘Ziegler-Natta-catalyst’, e.g. for the polymerization of alkenes and organosilicon compounds, and as a precursor of reagents in organic synthesis (Haiduc and Zuckerman, 1985).

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References

  • Adamson, R. H., Canellos, G. R. and Sieber, S. M. (1975) Studies on the antitumor activity of gallium nitrate (NSC-15200) and other group IIIa metal salts. Cancer Chemother. Rep., Part 1, 59, 599–610.

    Google Scholar 

  • Berdel, W. E., Schmoll, H. J., Scheulen, M. E. et al. (1993) Phase I evaluation of the new antineoplastic compound titanocene dichloride in adults with solid tumors. Onkologie, 16 (Suppl. 3), R172.

    Article  Google Scholar 

  • Berners-Price, S. J., Mirabelli, C. K., Johnson, R. K. et al. (1986) In vivo antitumor activity and in vitro cytotoxic properties of bis[l,2-bis(diphenylphos-phino)ethane]gold(I) chloride. Cancer Res., 46, 5486–5493.

    PubMed  CAS  Google Scholar 

  • Bischoff, H., Berger, M. R., Keppler, B. K. and Schmähl, D. (1987) Efficacy of β-diketonato complexes of titanium, zirconium, and hafnium against chemically induced autochthonous colonic tumors in rats. J. Cancer Res. Clin. Oncol., 113, 446–450.

    Article  PubMed  CAS  Google Scholar 

  • Calabresi, P. and Parks, R. E. (1975) Chemotherapy of neoplastic diseases, in The Pharmacological Basis of Therapeutics, 5th edn (eds L. S. Goodman and A. Gilman), Macmillan Publ. Co. Inc., New York, pp. 1248–1395.

    Google Scholar 

  • Clearfield, A., Warner, D. K., Saldarriaga-Molina, C. H. et al. (1975) Structural studies of (π-C5H5)2MX2 complexes and their derivatives. The structure of bis(π-cyclopentadienyl)titanium dichloride. Can. J. Chem., 53, 1622–1629.

    Article  CAS  Google Scholar 

  • Crowe, A. J. and Smith, P. J. (1984) Investigations into the antitumour activity of organotin compounds. 2. Diorganotin dihalide and dipseudohalide complexes. Inorg. Chim. Acta, 93, 179–184.

    Article  CAS  Google Scholar 

  • Crowe, A. J., Smith, P. J. and Atassi, G. (1980) Investigations into the antitumour activity of organotin compounds. I. Diorganotin dihalide and dipseudohalide complexes. Chem.-Biol. Interact., 32, 171–178.

    Article  PubMed  CAS  Google Scholar 

  • Elo, H. O. and Lumme, P. O. (1985) Antitumor activity of trans-bis (salicylaldoxi-mato) copper(II): a novel antiproliferative metal complex. Cancer Treat. Rep., 69, 1021–1022.

    PubMed  CAS  Google Scholar 

  • Garzon, F. T., Berger, M. R., Keppler, B. K. and Schmähl, D. (1987) Comparative antitumor activity of ruthenium derivatives with 5′-deoxy-5-fluorouridine in chemically induced colorectal tumors in SD rats. Cancer Chemother. Pharmacol, 19, 347–349.

    Article  PubMed  CAS  Google Scholar 

  • Goldin, A. and Wolpert-DeFilippes, M. K. (1979) Nude mouse models as predictors of chemotherapy in man: thymidine and pyrimidines. Bull. Cancer (Paris), 66, 61–66.

    CAS  Google Scholar 

  • Gowik, P., Klapötke, T. and Pickardt, J. (1989) Quantitative oxidation of organovanadium(IV) and-niobium(IV) complexes: synthesis of Cp2V(SbF6)2, [Cp2VCl2][AsF6], [Cp2V(AsF6)2][AsF6]. Crystal structure of [Cp2NbCl2][SbF6]. Organometallics, 8, 2953–2956.

    Article  CAS  Google Scholar 

  • Gowik, P., Klapötke, T. and Tornieporth-Oetting, I. (1989) Dichlorobis(-η5-cy clopentadienyl)rhenium (VII) tris(hexafluoroantimonat): Synthese des ersten Rhenocen(VII)-dichlorid-Kations. Chem. Ber., 122, 2273–2274.

    Article  CAS  Google Scholar 

  • Gowik, P., Klapötke, T. and White, P. (1989) Dikationen des Molybdänocen(VI)-und Wolframocen(VI)-dichlorids. Chem. Ber., 122, 1649–1650.

    Article  CAS  Google Scholar 

  • Haiduc, I. and Zuckerman, J. J. (1985) Basic Organometallic Chemistry. Walter de Gruyter, Berlin, New York.

    Book  Google Scholar 

  • Harstrick, A., Schmoll, H. J., Saϟ, G. et al. (1993) Activity of a novel metal compound, titanocen-dichloride, in cisplatin and doxorubicin resistant human ovarian carcinoma cell lines. Eur. ]. Cancer, 29A, 1000–1002.

    Article  CAS  Google Scholar 

  • Heim, M. E., Bischoff, H. and Keppler, B. K. (1990) Clinical studies with budotitane-a new non-platinum complex for cancer therapy, in Metal Ions in Biology and Medicine (eds P. Collery, L. A. Poirier, M. Manfait and J. C. Etienne), John Libbey Eurotext, Paris, pp. 508–510.

    Google Scholar 

  • Hervada, T., Guglietta, A., Nardi, R. V. and Brown, H. R. (1990) Gastric lesions induced by titanocene dichloride in rats. Gastroenterology, 98, A58.

    Google Scholar 

  • Keppler, B. K. and Schmähl, D. (1986) Preclinical evaluation of dichlorobis(l-phenylbutane-l,3-dionato)titanium(IV) and budotitane. Arzneim.-Forsch./ Drug Res., 36, 1822–1828.

    CAS  Google Scholar 

  • Keppler, B. K., Berger, M. R. and Heim, M. E. (1990) New tumor-inhibiting metal complexes. Cancer Treat. Rev., 17, 261–277.

    Article  PubMed  CAS  Google Scholar 

  • Keppler, B. K., Diez, A. and Scifried, V. (1985) Antitumor activity of phenyl substituted dihalogenobis(l-phenyl-l,3-butanedionato)titanium(IV) compounds. Arzneim.-Forsch./Drug Res., 35, 1832–1836.

    CAS  Google Scholar 

  • Keppler, B. K., Friesen, C., Moritz, H. G. et al. (1991) Tumor-inhibiting bis(β-diketonato)metal complexes. Budotitane, cis-diethoxybis(l-phenylbutane-l, 3-dionato)titanium(IV). The first transition metal complex after platinum to qualify for clinical trials. Struct. Bond., 78, 97–127.

    Article  CAS  Google Scholar 

  • Köpf, H. and Köpf-Maier, P. (1979) Titanocen-dichlorid-das erste Metallocen mit canceros ta tischer Wirksamkeit. Angezv. Chetn., 91, 509–510; Angew. Chem. Int. Ed. Engl, 18, 477.

    Article  Google Scholar 

  • Köpf-Maier, P. (1985) Glucocorticoid induction of cleft palate after treatment with titanocene dichloride? Toxicology, 37, 111–116.

    Article  PubMed  Google Scholar 

  • Köpf-Maier, P. (1987) Tumor inhibition by titanocene complexes: influence upon two xenografted human lung carcinomas. J. Cancer Res. Clin. Oncol., 113, 342–348.

    Article  PubMed  Google Scholar 

  • Köpf-Maier, P. (1989) Tumor inhibition by titanocene complexes: influence on xenografted human adenocarcinomas of the gastrointestinal tract. Cancer Chemother. Pharmacol, 23, 225–230.

    Article  PubMed  Google Scholar 

  • Köpf-Maier, P. (1990) Intracellular localization of titanium with xenografted sensitive human tumors after treatment with the antitumor agent titanocene dichloride. J. Struct. Biol, 105, 35–45.

    Article  PubMed  Google Scholar 

  • Köpf-Maier, P. and Funke-Kaiser, P. (1986) Organ toxicity of metallocene dichlorides. The effect of (C5H5)2TiCl2 and (C5H5)2VCl2 on renal structure. Toxicology, 38, 81–90.

    Article  PubMed  Google Scholar 

  • Köpf-Maier, P. and Gerlach, S. (1986a) Pattern of toxicity by titanocene dichloride in mice. Blood and urine chemical parameters.J. Cancer Res. Clin. Oncol., 111, 243–247.

    Article  PubMed  Google Scholar 

  • Köpf-Maier, P. and Gerlach, S. (1986b) Pattern of toxicity by titanocene dichloride in mice. Hematologic parameters. Anticancer Res., 6, 235–240.

    PubMed  Google Scholar 

  • Köpf-Maier, P. and Klapötke, T. (1992a) Antitumor activity of ionic niobocene and molybdenocene complexes in high oxidation states. J. Cancer Res. Clin. Oncol., 118, 216–221.

    Article  PubMed  Google Scholar 

  • Köpf-Maier, P. and Klapötke, T. (1992b) Ionic rhenocene derivatives with antitumor activity. Cancer Chemother. Pharmacol, 29, 361–366.

    Article  PubMed  Google Scholar 

  • Köpf-Maier, P. and Köpf, H. (1979) Vanadocen-dichlorid-ein weiteres Antitumor-Agens aus der Metallocenreihe. Z. Naturforsch., 34b, 805–807.

    Google Scholar 

  • Köpf-Maier, P. and Köpf, H. (1986) Antitumor metallocenes: new developments and toxicologic features. Anticancer Res., 6, 227–234.

    PubMed  Google Scholar 

  • Köpf-Maier, P. and Köpf, H. (1987) Tumor inhibition by titanocene complexes. Activity against B16 melanoma and colon 38 carcinoma. Arzneim.-Forsch./ Drug Res., 37, 532–534.

    Google Scholar 

  • Köpf-Maier, P. and Köpf, H. (1988) Transition and main-group metal cyclo-pentadienyl complexes: preclinical studies on a series of antitumor agents of different structural type. Struct. Bond., 70, 103–185.

    Article  Google Scholar 

  • Köpf-Maier, P. and Martin, R. (1989) Subcellular distribution of titanium in the liver after treatment with the antitumor agent titanocene dichloride. Virch. Arch. B Cell Pathol, 57, 213–222.

    Article  Google Scholar 

  • Köpf-Maier, P., Brauchle, U. and Henssler, A. (1988) Organ distribution and pharmacokinetics of titanium after treatment with titanocene dichloride. Toxicology, 51, 291–298.

    Article  PubMed  Google Scholar 

  • Köpf-Maier, P., Hesse, B. and Köpf, H. (1980) Tumorhemmung durch Metallocene: Wirkung von Titanocen-, Zirconocen-und Hafnocen-dichlorid gegenüber Ehrlich-Aszites-Tumor der Maus. J. Cancer Res. Clin. Oncol., 96, 43–51.

    Article  PubMed  Google Scholar 

  • Köpf-Maier, P., Janiak, C. and Schumann, H. (1988) Antitumor properties of organometallic metallocene complexes of tin and germanium. J. Cancer Res. Clin. Oncol., 114, 502–506.

    Article  PubMed  Google Scholar 

  • Köpf-Maier, P., Köpf, H. and Neuse, E. W. (1984) Ferricenium complexes: a new type of water-soluble antitumor agent. J. Cancer Res. Clin. Oncol., 108, 336–340.

    Article  PubMed  Google Scholar 

  • Köpf-Maier, P., Leitner, M. and Köpf, H. (1980) Tumor inhibition by metal-locenes: antitumor activity of niobocene and tungstocene dichlorides. J. Inorg. Nucl. Chetn., 42, 1789–1791.

    Article  Google Scholar 

  • Köpf-Maier, P., Leitner, M., Voigtländer, R. and Köpf, H. (1979) Molybdenocen-dichlorid als Antitumor-Agens. Z. Naturforsch., 34c, 1174–1176.

    Google Scholar 

  • Köpf-Maier, P., Neuse, E., Klapötke, T. and Köpf, H. (1989) Ionic titanocene complexes: a new type of antitumor agent. Cancer Chemother. Pharmacol, 24, 23–27.

    Article  PubMed  Google Scholar 

  • Kumano, N., Nakai, Y., Ishikawa, T. et al. (1978) Effect of carboxyethyl-germanium sesquioxide on the methylcholanthrene-induced tumorigenesis in mice. Sci. Rep. Res. Inst. Tohoku Univ., Ser. A, 25, 89–95.

    CAS  Google Scholar 

  • Mulinos, M. G. and Amin, P. (1980) Toxicology and phase I study of a new anticancer agent, spirogermanium HC1. Proc. Fed. Am. Soc. Exp. Biol, 39, 747.

    Google Scholar 

  • Murthy, M. S., Rao, L. N., Kuo, L. Y. et al. (1988) Antitumor and toxicologic properties of the organometallic anticancer agent vanadocene dichloride. Inorg. Chim. Acta, 152, 117–124.

    Article  CAS  Google Scholar 

  • Rehder, D. (1991) Bioanorganische Chemie des Vanadiums. Angew. Chem., 103, 152–172.

    Article  CAS  Google Scholar 

  • Rosenberg, B. (1973) Platinum coordination complexes in cancer chemotherapy. Naturwissenschaften, 60, 399–406.

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg, B., VanCamp, L., Trosko, J. E. and Mansour, V. H. (1969) Platinum compounds: a new class of potent antitumor agents. Nature, 222, 385–486.

    Article  PubMed  CAS  Google Scholar 

  • Sava, G., Zorzet, S., Giraldi, T. et al. (1984) Antineoplastic activity and toxicity of an organometallic complex of ruthenium(II) in comparison with cis-PDD in mice bearing solid malignant neoplasms. Eur. ]. Cancer Clin. Oncol., 20, 841–847.

    Article  CAS  Google Scholar 

  • Sekar, N. and Govindasamy, S. (1991) Insulin mimetic role of vanadate on plasma membrane insulin-receptors. Biochem. Internat., 23, 461–466.

    Article  CAS  Google Scholar 

  • Thewalt, U., Berhalter, K. and Neuse, E. W. (1985) The crystal and molecular structure of acetonitrilechlorodicyclopentadienyltitanium tetrachlorofer-rate(III). Some Mössbauer and X-ray photoelectron spectroscopic data. Trans. Met. Chem., 10, 393–395.

    Article  CAS  Google Scholar 

  • Toney, J. H., Murthy, M. S. and Marks, T. J. (1985) Biodistribution and pharmacokinetics of vanadium following intraperitoneal administration of vanadocene dichloride to mice. Chem. Biol. Interact., 56, 45–54.

    Article  PubMed  CAS  Google Scholar 

  • Venditti, J. M. (1981) Preclinical drug development: rationale and methods. Semin. Oncol., 8, 349–361.

    PubMed  CAS  Google Scholar 

  • Von Hoff, D. D., Schilsky, R., Reichert, C. M. et al. (1979) Toxic effects of cis-dichlorodiammineplatinum(II)in man. Cancer Treat. Rep., 63, 1527–1531.

    Google Scholar 

  • Wilkinson, G. and Birmingham, J. M. (1954) Bis-cyclopentadienyl compounds of Ti, Zr, V, Nb and Ta. J. Am. Chem. Soc., 76, 4281–4284.

    Article  CAS  Google Scholar 

  • Wolpert-DeFilippes, M. K. (1979) Antitumor activity of cis-dichlorodiammine-platinum(II). Cancer Treat. Rep., 63, 1453–1458.

    PubMed  CAS  Google Scholar 

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Authors
  1. P. Köpf-Maier
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  2. H. Köpf
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  1. Johnson Matthey Technology Centre, Reading, UK

    Simon P. Fricker

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Köpf-Maier, P., Köpf, H. (1994). Organometallic titanium, vanadium, niobium, molybdenum and rhenium complexes — early transition metal antitumour drugs. In: Fricker, S.P. (eds) Metal Compounds in Cancer Therapy. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-1252-9_6

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  • DOI: https://doi.org/10.1007/978-94-011-1252-9_6

  • Publisher Name: Springer, Dordrecht

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