Anti-tumor activity of Titanocene Y in xenografted Caki-1 tumors in mice

Fichtner, Iduna; Pampillón, Clara; Sweeney, Nigel J.; Strohfeldt, Katja; Tacke, Matthias

doi:10.1097/00001813-200603000-00012

Cited by 66 publications

(38 citation statements)

References 24 publications

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“…[24] Furthermore, very successful animal studies with the use of titanocene Y on Caki-1 tumor-bearing mice and xenograft Ehrlich's ascites tumor in mice were performed. [25,26] The main idea behind the research presented in this paper was to convert the methoxy group of titanocene Y, our most cytotoxic titanocene, into a glycol methyl ether or glycol amine side chain in order to improve the cytotoxicity and availability in the cell. Within this paper, we present the synthetic possibilities and limits of introducing a glycol methyl ether or a glycol amine group in all three mentioned classes of titanocenes and comparing the antiproliferative effects of the new synthesised titanocenes.…”

Section: Introductionmentioning

confidence: 99%

Glycol Methyl Ether and Glycol Amine Substituted Titanocenes as Antitumor Agents

et al. 2006

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Abstract6‐[4‐(2‐Methoxyethoxy)phenyl]fulvene (3a) and 6‐{4‐[2‐(dimethylamino)ethoxy]phenyl}fulvene (3b) were prepared as the starting materials for the synthesis of three different classes of titanocenes, which are ansa‐titanocenes, diarylmethyl‐substituted titanocenes and benzyl‐substituted titanocenes. Because the synthetic possibilities seem to be limited, only ansa‐titanocene {1,2‐bis(cyclopentadienyl)‐1,2‐bis[4‐(2‐methoxyethoxy)phenyl]ethanediyl}titanium dichloride (4a) and benzyl‐substituted titanocene bis‐{[4‐(2‐methoxyethoxy)benzyl]cyclopentadienyl}titanium(IV) dichloride (6a) were obtained and characterised. The change in the substitution pattern of the phenyl moiety from an oxygen atom to a nitrogen atom had such a big influence on the reaction that not one compound of the three titanocene classes could be synthesised, and it was also not possible to obtain diarylmethyl‐substituted titanocenes with the use of either of the fulvenes. When benzyl‐substituted titanocene 6a was tested against pig kidney cells (LLC‐PK), an antiproliferative effect that results in an IC50 value of 43 μM, was observed. This IC50 value is in the lower range of the cytotoxicities evaluated for titanocenes up to now. ansa‐Titanocene 4a surprisingly showed, when tested on the same cell line, a proliferative effect together with a fast rate of hydrolysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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Section: Introductionmentioning

confidence: 99%

Glycol Methyl Ether and Glycol Amine Substituted Titanocenes as Antitumor Agents

et al. 2006

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“…108, 109 Their effects on the immune system were found and they are assumed to be capable of activating apoptosis in cancer cells. [110][111][112] The anticancer activity in a series of ferrocene deriva tives was found for the first time in ferrocenium salts with hard anions, such as tetrachloroferrate(II), picrate, and trichloroacetae. 73,74 Ferrocene and inorganic iron(III) salts with the same anions were inactive.…”

Section: Methodsmentioning

confidence: 99%

Ferrocenes as potential anticancer drugs. Facts and hypotheses

et al. 2014

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We analyzed the research data on antitumor effects of a wide range of ferrocene compounds and discussed possible mechanisms of their bioactivities. Current trends in the study of antican cer effects of ferrocene derivatives were considered. Promising ways in the design of low toxicity anticancer ferrocene based drugs of new generation were outlined. * Dedicated to the 60th anniversary of the A. N. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences (INEOS RAS). The review was written on the initiative and with the active participation of Yu. S. Nekrasov who served with good faith and fidelity for INEOS RAS for more than 40 years. † Deceased.

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“…These results were underlined by first mechanistic studies concerning the effect of these titanocenes on apoptosis and the apoptotic pathway in prostatecancer cells [23]. Furthermore, first animal studies have been published recently reporting the successful treatment of xenografted Ehrlichs ascites tumor in mice with an ansa-titanocene [24] and xenografted Caki-1 [25], A431 [26], and MCF-7 [27] tumors with titanocene Y. The effect of titanocene Y against xenograft Caki-1 tumors in mice was shown to be superior to cis-platin and in the MCF-7 experiment, the tumors could even be shrunk by titanocene Y.…”

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confidence: 91%

Synthesis and Cytotoxicity Studies of New (Dimethylamino)‐Functionalised and 7‐Azaindole‐Substituted ‘Titanocene’ Anticancer Agents (7‐Azaindole=1H‐Pyrrolo[2,3‐b]pyridine)

Hogan

Cotter

Claffey

et al. 2008

Helvetica Chimica Acta

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From the carbolithiation of 1-(cyclopenta-2,4-dien-1-ylidene)-N,N-dimethylmethanamine (¼ 6-(dimethylamino)fulvene; 3) and different lithiated azaindoles 2 (1-methyl-7-azaindol-2-yl, 1-[(diethylamino)methyl]-7-azaindol-2-yl, and 1-(methoxymethyl)-7-azaindol-2-yl), the corresponding lithium cyclopentadienide intermediates 4a -4c were formed (7-azaindole ¼ 1H-pyrrolo[2,3-b]pyridine). The latter underwent a transmetallation reaction with TiCl 4 resulting in the (dimethylamino)-functionalised titanocenes 5a -5c. When the titanocenes 5a -5c were tested against LLC-PK cells, the IC 50 values obtained were of 8.8, 12, and 87 mm, respectively. The most cytotoxic titanocene, 5a, with an IC 50 value of 8.8 mm is nearly as cytotoxic as cis-platin, which showed an IC 50 value of 3.3 mm when tested on the epithelial pig kidney LLC-PK cell line, and ca. 200 times better than titanocene dichloride itself.Introduction. -Titanium-based reagents have significant potential activity against solid tumors. Budotitane (¼ cis-diethoxybis(1-phenylbutane-1,3-dionato)titanium(IV)) looked very promising during its preclinical evaluation but did not go beyond phase-I clinical trials, although a Cremophor EL based formulation was found for this rapidly hydrolyzing molecule [18 -20] allow direct access to highly substituted titanocenes via reductive dimerisation, carbolithiation, or hydridolithiation of the fulvene followed by transmetallation in the last two cases.Titanocene Y (¼ dichloridobis{ (1,2,3,4,5-h)-1-[(4-methoxyphenyl)methyl]cyclopenta-2,4-dien-1-yl}titanium), which has an IC 50 value of 21 mm when tested on the LLC-PK cell line, was synthesised through hydridolithiation of 6-(p-anisyl)fulvene and Superhydride (Li[BEt 3 H]) followed by transmetallation with TiCl 4 [12]. The antiproliferative activity of titanocene Y has been studied in 36 human tumor cell lines [21] and in explanted human tumors [22]. These in vitro and ex vivo experiments showed that prostate, cervix, and renal cell cancer are prime targets for these novel classes of titanocenes, whereas the IC 50 values for the breast-cancer cell lines were very

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Anti-tumor activity of Titanocene Y in xenografted Caki-1 tumors in mice

Cited by 66 publications

References 24 publications

Glycol Methyl Ether and Glycol Amine Substituted Titanocenes as Antitumor Agents

Glycol Methyl Ether and Glycol Amine Substituted Titanocenes as Antitumor Agents

Ferrocenes as potential anticancer drugs. Facts and hypotheses

Synthesis and Cytotoxicity Studies of New (Dimethylamino)‐Functionalised and 7‐Azaindole‐Substituted ‘Titanocene’ Anticancer Agents (7‐Azaindole=1H‐Pyrrolo[2,3‐b]pyridine)

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