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H Köpf

Publications and source records attributed to H Köpf.

9 recordsLinked to original sources
PubMed1989

Ionic titanocene complexes: a new type of antitumor agent.

Five ionic cyclopentadienyltitanium (IV) derivatives were investigated for their activity against fluid Ehrlich ascites tumor. Four compounds were built up by the intact bis(cyclopentadienyl)titanium(IV) ("titanocene") unit, forming the cationic moiety together with two covalently bound ligands, with certain anions being bonded via electrostatic forces: the acetonitrile complex [(C5H5)2TiCl(NCCH3)]+[FeC14]- (I), the 2'2'-bipyridyl derivative [(C5H5)2Ti(bipy)]2+[CF3SO3]2 (II), the o-phenanthroline complex [(C5H5)2Ti(phen)]2+[CF3SO3]2 (III), and the N-methyl-o-aminothiophenolate derivative [(C5H5)2Ti[o-S(NACH3)C6H4]]+I- (IV). Another ionic cyclopentadienyltitanium derivative investigated was the five-coordinate bis(dithiolene) chelate (C5H5)Ti(1,2,4-S2C6H3CH3)2]-N(C2H5)4)+ (V), the cyclopentadienyltitanium moiety representing the anionic part of the complex salt. All complexes were ionic, salt-like compounds, distinguished by good water solubility. Whereas complexes I, III, and V, given at optimal dose levels, effected maximal cure rates of only 70%-80%, all animals were cured after receiving complexes II and IV at dose ranges of 200-220 and 240-300 mg/kg, respectively. The antitumor activity of complex I was confirmed against solid experimental tumor systems B16 melanoma, colon 38 carcinoma, and Lewis lung carcinosarcoma. Because of their improved solubility in water and pronounced antitumor activity (especially that of II and IV against fluid Ehrlich ascites tumor), ionic cyclopentadienyl titanium complexes are considered to be an interesting new type of antitumor agent.

Animals↗
PubMed1987

Tumor inhibition by titanocene complexes. Activity against B16 melanoma and colon 38 carcinoma.

In the present study, the antitumor activity of some titanocene derivatives (C5H5)2TiX2 (I, X = Cl; II, X = Br; III, X = cis-OOCCH = CHCOOH; IV, X = p-SC6H4NH3+Cl-) was investigated against B16 melanoma and colon 38 carcinoma. Both tumors grew subcutaneously as solid tumors in mice. Substances were applied intraperitoneally either as single, triple or 5-fold injections. Against both tumors, satisfactory results were observed for the chloro, bromo and aminothiophenolato derivatives I, II and IV, resp. They reduced tumor growth by 60-80% to 40-20% of control values. These effects underline the antitumor potency of titanocene complexes and show that titanocene dihalides as well as titanocene derivatives containing hydrophilic ligands X are able to inhibit the growth of various solid experimental tumors.

Animals↗
PubMed1986

[Cytostatic platinum complexes: an unexpected discovery with considerable consequences].

Antineoplastic platinum complexes represent new-developed inorganic cytostatics, which interfere with intracellular nucleic acids, especially with DNA. The main representative is cis-diamminedichloroplatinum (II) (cis-platin, DDP). It has proven effective against human urogenital tumors and against carcinomas of the head and neck. The most severe side effects are nephrotoxicity and gastrointestinal irritation. Stimulated by the clinical success of cisplatin, a series of platinum complexes of the second generation has been recently developed. Moreover, anti-tumor properties were detected for various organometallic complexes containing titanium, vanadium, tin, or iron as central atoms.

Antineoplastic Agents↗
PubMed1985

Activity of titanocene dihalides against a human colon carcinoma heterotransplanted to athymic mice.

The antitumor activity of cis-diamminedichloroplatinum (II) and of two metallocene derivatives, titanocene dichloride (C5H5)2TiCl2 and titanocene dibromide (C5H5)2TiBr2, was investigated against a human colon adenocarcinoma heterotransplanted to athymic mice. The substances were administered at various doses on a Q2DX5 or a Q3DX5 schedule. Whereas cis-diamminedichloroplatinum (II) induced an only marginal tumor-inhibiting effect, both titanocenes markedly suppressed tumor development (T/C values: 23-40%) and caused stagnation and relative decrease of tumor growth, when they were applied in subtoxic doses far below the LD10 level. The results are remarkable with respect to the general insensitivity of human colorectal carcinomas to cytostatic agents.

Adenocarcinoma↗
PubMed1984

Ferricenium complexes: a new type of water-soluble antitumor agent.

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]- X 2H2O, [2,4,6-(NO2)3C6H2O]-, or [CCl3COO]- X 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.

Animals↗
PubMed1979

[Molybdocene dichloride as an antitumor agent (author's transl)].

The antitumor activity of molybdocene dichloride is tested against Ehrlich ascites tumor in CF1 mice. The application of 75 of 100 mg/kg 24 h after transplantation achieves 100% tumor inhibition until day 30. Following the d0 and d1 metallocene dichlorides of titanium and vanadium, molybdocene dichloride is the first analogous d2 system revealing similar antineoplastic properties.

Animals↗
PubMedDate not supplied

Antitumor metallocenes: new developments and toxicologic features.

Recent results concerning new antitumor metallocene derivatives have shown that not only numerous titanocene dihalides and bis(pseudohalides) exhibit antiproliferative activity, but that also some titanocene complexes (C5H5)2TiX2 containing carboxylates or hydrochlorinated aminothiophenolates as ligands X, are characterized by pronounced antineoplastic efficacy. Whereas antitumor activity of metallocene derivatives has originally been established against Ehrlich ascites tumor, recent experimental results demonstrate antiproliferative activity also against B16 melanoma, sarcoma 180, as well as against human tumors heterotransplanted to athymic mice. Studies upon the organ toxicity of titanocene dichloride indicate a pattern of toxicity markedly differing from that observed after treatment with cytostatic platinum compounds.

Animals↗
PubMedDate not supplied

Tumor inhibition by titanocene complexes: activity against sarcoma 180.

The antitumor activity of various titanocene derivatives was examined against ascitic and solid, subcutaneously growing sarcoma 180. The complexes investigated were two dihalide compounds, (C5H5)2TiCl2 (I) and (C5H5)2TiBr2 (II), two carboxylato complexes, (C5H5)2Ti (cis-OOCCH = CHCOOH)2(III) and (C5H5)2Ti(OOCCCl3)2(IV), and the p-aminothiophenolate hydrochloride (C5H5)2Ti(p-SC6H4NH3+Cl-)2(V). Against ascitic sarcoma 180, best results were obtained for I; an injection of 50 mg/kg resulted in the survival of 40-50% of the animals (ILS, 161-184%). A similar result was recorded for cis-diamminedichloroplatinum(II), whereas the compounds II-IV induced a maximum cure rate of 20% (ILS, 95-139%). Against solid sarcoma 180, triple injections of I-V caused reduction of mean tumor weight to 23-53% of control values, the dichloro complex I exhibiting most pronounced activity. These results clearly underline antitumor potency for titanocene complexes (C5H5)2TiX2 modified at the acido ligand X.

Animals↗