Summary
The antitumor activity of the four metallocene compounds decaphenylstannocene [η5-(C6H5)5C5]2Sn(II), decabenzylstannocene [η5-(C6H5CH2)5C5]2Sn(II), decaphenylgermanocene [η5-(C6H5)5C5]2Ge(II), and decabenzylgermanocene [η5-(C6H5CH2)5C5]2Ge(II), containing the main group IV elements tin or germanium as the central metal atom and two pentasubstituted cyclopentadienyl ring ligands in sandwich arrangement, were tested against Ehrlich ascites tumor in female CF1 mice. The complexes caused cure rates of 40% to 90% of the animals treated over rather broad dose ranges. With both germanocene complexes, no strong dose-activity relationship was manifest. The toxicity of all four metallocenes was low, the LD10 values of both stannocenes being 460 and 500 mg/kg, and those of both germanocenes higher than 700 mg/kg. Regarding the isolated pentasubstituted cyclopentadiene ligands (C6H5)5C5H and (C6H5CH2)5C5H, these also exhibited antitumor activity which was less pronounced than that of the metal-containing sandwich complexes. Decasubstituted stannocene and germanocene compounds represent a new type of non-platinum group metal antitumor agents structurally differing from known inorganic and organometallic cytostatics.
Similar content being viewed by others
References
Berners-Price SJ, Mirabelli CK, Johnson PK, Mattern MR, McCabe FL, Faucette LF, Sung CM, Mong SM, Sadler PJ, Crooke ST (1986) In vivo antitumor activity and in vitro cytotoxic properties of bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride. Cancer Res 46:5486–5493
Cleare MJ, Hydes PC, Malerbi BW, Watkins DM (1978) Anti-tumour platinum complexes: relationships between chemical properties and activity. Biochimie 60:835–850
Crowe AJ, Smith PJ, Atassi G (1980) Investigations into the antitumor activity of organotin compounds. I. Diorganotin dihalide and di-pseudohalide complexes. Chem Biol Interact 32:171–178
Crowe AJ, Smith PJ, Atassi G (1984) Investigations into the antitumour activity of organotin compounds. II. Diorganotin dihalide and dt-pseudohalide complexes. Inorg Chim Acta 93:179–184
Elo HO, Lumme PO (1985) Antitumor activity of trans-bis(salicylaldoximato)copper(II): a novel antiproliferative metal complex. Cancer Treat Rep 69:1021–1022
Fairlie DP, Whitehouse MW, Broomhead JA (1987) Irritancy and anti-inflammatory activity of bis[η5-cyclopentadienyl)titanium(IV) complexes in rats. Chem Biol Interact 61:277–291
Heeg MJ, Janiak C, Zuckerman JJ (1984) Decaphenylstannocene, [η5-(C6H5)5C5]2Sn(II): the first symmetrical main-group sandwich compound. J Am Chem Soc 106:4259–4261
Keller HJ, Keppler B, Schmähl D (1982) Antitumor activity of cis-dihalogenobis(1-phenyl-1,3-butanedionato)titanium(IV) compounds against Walker 256 carcinosarcoma. Arzneim Forsch/Drug Res 32:806–807
Köpf H, Köpf-Maier P (1979) Titanocen-dichlorid — das erste Metallocen mit cancerostatischer Wirksamkeit. Angew Chem 91:509; Angew Chem Int Ed Engl 18:477–478
Köpf-Maier P, Köpf H (1979) Vanadocen-dichlorid — ein weiteres Antitumor-Agens aus der Metallocenreihe. Z Naturforsch 34b:805–807
Köpf-Maier P, Köpf H (1986) Metallocene complexes: organometallic antitumor agents. Drugs Fut 11:297–319
Köpf-Maier P, Köpf H (1987a) Non-platinum-group metal antitumor agents: history, current status and perspectives. Chem Rev 87:1137–1152
Köpf-Maier P, Köpf H (1987b) Tumorhemmende Cyclopentadienyl-Komplexe: experimentelle Untersuchungen zur Überprüfung der Cyclopentadien-Hypothese. J Organomet Chem 342:167–176
Köpf-Maier P, Hesse B, Voigtländer R, Köpf H (1980) 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
Köpf-Maier P, Köpf H, Neuse EW (1984) Ferricenium complexes — a new type of water-soluble antitumor agents. J Cancer Res Clin Oncol 108:336–340
Kumano N, Nakai Y, Ishikawa T, Koinumaru S, Suzuki S, Konno K (1978) Effect of carboxyethylgermanium sesquioxide on the methylcholanthrene-induced tumorigenesis in mice. Sci Rep Res Inst Tohoku Univ 25:89–95
Mirabelli CK, Johnson RK, Sung CM, Faucette L, Muirhead K, Crooke ST (1985) Evaluation of the in vivo antitumor activity and in vitro cytotoxic properties of auranofin, a coordinated gold compound, in murine tumor models. Cancer Res 45:32–39
Mulinos MG, Amin P (1980) Toxicology and phase I study of a new anticancer agent, spirogermanium HC1. Fed Am Soc Exp Biol 39:747
Rice L, Wheeler JW, Geschickter CF (197) Spirans XXII. Synthesis of 4,4-dialkyl-4-germacyclohexanone and 8,8-dialkyl-8-germaazaspiro(4,5)decanes. J Heterocyclic Chem 11:1041–1047
Rosenberg B (1978) Platinum complex-DNA interactions and anticancer activity. Biochimie 60:859–867
Schumann H, Janiak C, Hahn E, Loebel J, Zuckermann JJ (1985) Decabenzylgermanocen: Synthese und Struktur eines monomeren, luftstabilen Germanocens. Angew Chem 97:765; Angew Chem Int Ed Engl 24:733
Schumann H, Janiak C, Hahn E, Kolax C, Loebel J, Rausch MD, Zuckermann JJ, Heeg MJ (1986) Decabenzylgermanocen,-stannocen und-plumbocen. Synthese und Struktur von luftstabilen Metallocenen der 4. Hauptgruppe des Periodensystems der Elemente. Chem Ber 119:2656–2667
Tsutsui M, Kakimoto N, Darrell DA (1981) Crystal structure of “carboxyethylgermanium sesquioxide”. J Am Chem Soc 98:8287–8289
Weiss GR, Kisner DL, Kuhn JG, Melink TJ, Myers JW, Von Hoff DD (1984) Miscellaneous anticancer drugs. In: Pinedo HM, Chabner BA (eds) Cancer chemotherapy annual 6. Elsevier, New York, pp 163–169
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Köpf-Maier, P., Janiak, C. & Schumann, H. Antitumor properties of organometallic metallocene complexes of tin and germanium. J Cancer Res Clin Oncol 114, 502–506 (1988). https://doi.org/10.1007/BF00391500
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00391500