Summary
The antitumor activity of a series of iron complexes, i.e., of ferrocene [Cp2Fe], of tetrachloroferrates(III) [R4N]+[FeCl4]-, and of ferricenium complexes [Cp2Fe]+X- (X-=[FeCl4]-, 1/2[Cl3FeOFeCl3]2-, [H5Mo7O24]-·2H2O, [2,4,6-(NO2)3C6H2O]-, or [CCl3COO]-·2 CCl3COOH) was investigated against EAT in CF1 mice. Whereas ferrocene and the ammonium tetrachloroferrates(III) did not show recognizable tumor-inhibiting activity, such activity was exhibited by the water-soluble, salt-like ferricenium complexes; the best antineoplastic properties, with optimum cure rates of 100%, were found for ferricenium picrate and ferricenium trichloroacetate.
The ferricenium compounds are the first iron complexes for which antineoplastic activity has now been shown. They represent a new type of antitumor agent insofar as they differ fundamentally from known inorganic and organometallic antitumor agents (a) by their ionic, salt-like character, which is responsible for their high water solubility, and (b) by the absence of a cis-dihalometal moiety; this moiety has been recognized as important for the intracellular action of other known inorganic cytostatics.
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Abbreviations
- Cp:
-
C5H5, cyclopentadienyl ring ligand
- EAT:
-
Ehrlich ascites tumor
- IP:
-
intraperitoneal(ly)
- p.t.t.:
-
post transplantationem tumoris
References
Boeyens JCA, Lalloo PC, Neuse EW, Wei HH (1984) A reinvestigation of the ferrocene oxidation by iron(III) chloride in 2-butanone/ethanol. S Afr J Chem (in press)
Churchill MR, Landers AG, Rheingold AL (1981) Crystal structure and molecular geometry of [(η5-C5H5)2Fe]2As4Cl10O2, the ferrocenium salt of a complex oxychloroarsenate(III) counterion. Inorg Chem 20:849–853
Cleare MJ (1974) Transition metal complexes in cancer chemotherapy. Coord Chem Rev 12:349–405
Cleare MJ, Hoeschele JD (1973) Studies on the antitumor activity of group VIII transition metal complexes. I. Platinum(II) complexes. Bioinorg Chem 2:187–210
Cleare MJ, Hydes PC, Malerbi BW, Watkins DM (1978) Anti-tumour platinum complexes: relationships between chemical properties and activity. Biochimie 60:835–850
Cleare MJ, Hydes PC, Hepburn DR, Malerbi BW (1980) Antitumor platinum complexes: structure-activity relationships. In: Prestayko AW, Crooke ST, Carter SK (eds) Cisplatin, current status and new developments. Academic, New York, pp 149–170
Clearfield A, Warner DK, Saldarriaga-Molina CH, Ropal R (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
Crowe AJ, Smith PJ, Atassi G (1980) Investigations into the antitumour activity of organotin compounds. I. Diorganotin dihalide and di-pseudohalide complexes. Chem Biol Interact 32:171–178
Green JC, Green MLH, Prout CK (1972) A bonding model for bent bis-(π-cyclopentadienyl) metal compounds. J Chem Soc Chem Commun 1972:421–422
Hendrickson DN, Sohn YS, Duggan DM, Gray HB (1973) Low-temperature (4.2 K) study of the 2E1u«2E2g band system in the electronic spectra of various ferricenium compounds. J Chem Phys 58:4666–4675
Keller HJ, Keppler B, Schmähl D (1983) Antitumor activity of cis-dihalogenobis(1-phenyl-1,3-butanedionato)titanium(IV) compounds. A new class of antineoplastic agents. J Cancer Res Clin Oncol 105:109–110
Köpf H, Köpf-Maier P (1979) Titanocen-dichlorid — das erste Metallocen mit cancerostatischer Wirksamkeit. Angew Chem 91:509; Angew Chem [Engl] 18:477–478
Köpf H, Köpf-Maier P (1983) Tumor inhibition by metallocene dihalides of early transition metals: chemical and biological aspects. ACS Symp Ser 209:315–333
Köpf-Maier P, Hesse B, Köpf H (1980a) Tumorhemmung durch Metallocene: Wirkung von Titanocen-, Zirconocen-und Hafnocen-dichlorid gegenüber Ehrlich-Aszites-Tumor der Maus. J Cancer Res Clin Oncol 96:43–51
Köpf-Maier P, Hesse B, Voigtländer R, Köpf H (1980b) Tumor inhibition by metallocenes: antitumor activity of titanocene dihalides (C5H5)2TiX2 (X=F, Cl, Br, I, NCS) and their application in buffered solutions as a method for suppressing drug-induced side effects. J Cancer Res Clin Oncol 97:31–39
Nesmejanow AN, Perewalowa EG, Jurjewa LP (1960) Unmittelbare Cyanierung der Ferriciniumsalze. Chem Ber 93:2729–2735
Neuse EW, Meirim MG (1984) Synthesis and spectroscopic features of bis(tetramethylammonium) and bis(benzyltriethylammonium) salts possessing a μ-oxo-bis(trichloroferrate) anion structure. Transition Metal Chem (in press)
Neuse EW (1984) Hydrophilic macromolecular ferricenium salts. I. Preparative and spectroscopic features of selected mononuclear ferricenium compounds. Adv Organomet Inorg Polymer Sci (in press)
Paulus EF, Schäfer L (1978) The crystal and molecular structure of ferricinium tetrachloroferrate. J Organomet Chem 144:205–213
Pavlik I, Klikorka J (1965) Infrared spectrum of the ferricenium cation. Coll Czech Chem Commun 30:664–674
Rosenberg B (1978) Platinum complex-DNA interactions and anticancer activity. Biochimie 60:859–867
Rosenberg B, VanCamp L, Trosko JE, Mansour VH (1969) Platinum compounds: a new class of potent antitumour agents. Nature 222:385–386
Wenzel M, Schneider M, Liss E (1979) Synthese, Organ-Verteilung und cytostatische Wirkung der N-Methyl-N-β-chloräthyl-hydrazone von Metallocen-aldehyden. Z Naturforsch [C] 34:670–676
Wilkinson G, Rosenblum M, Whiting MC, Woodward RB (1952) The structure of iron bis-cyclopentadienyl. J Am Chem Soc 74:2125–2126
Yashchenko GN, Shashmurina AA, Anoshina GM, Gorelova LA, Evstigneeva NG, Alekseeva LV, Radina LB (1978) Synthesis and study of the antineoplastic activity of ferrocene-containing compounds. Khim Farm Zh 12:68–72
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Supported by the Fonds der Chemischen Industrie and by Council, University of the Witwatersrand
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Köpf-Maier, P., Köpf, H. & Neuse, E.W. Ferricenium complexes: A new type of water-soluble antitumor agent. J Cancer Res Clin Oncol 108, 336–340 (1984). https://doi.org/10.1007/BF00390468
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DOI: https://doi.org/10.1007/BF00390468