Novel titanocene anti-cancer drugs derived from fulvenes and titanium dichloride (original) (raw)
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Applied Organometallic Chemistry, 2005
Starting from 2-furylfulvene (1a), 2-thiophenylfulvene (1b), and 1-methyl-2-pyrrolylfulvene (1c), [1,2-di(cyclopentadienyl)-1,2-di-(2-furyl)ethanediyl] titanium dichloride (2a), [1,2-di(cyclopentadienyl)-1,2-di-(2-thiophenyl)ethanediyl] titanium dichloride (2b), and [1,2-di(cyclopentadienyl)-1,2-bis-(1-methyl-2-pyrrolyl)ethanediyl] titanium dichloride (2c) were synthesized. When titanocenes (2a–c) were tested against pig kidney carcinoma cells (LLC-PK), inhibitory concentrations (50%) of 4.5 × 10−4M, 2.9 × 10−4M and 2.0 × 10−4M respectively were observed. Copyright © 2005 John Wiley & Sons, Ltd.
Journal of Inorganic Biochemistry, 2004
Starting from 6-(4 0 -methoxyphenyl)fulvene (1a), 6-(2 0 ,4 0 ,6 0 -trimethoxyphenyl)fulvene (1b), or 6- , and [1,2-di(cyclopentadienyl)-1,2-bis(3 0 ,5 0 -dimethoxyphenyl)ethanediyl] titanium dichloride (2c) were synthesised. When titanocenes 2a-c were tested against pig kidney carcinoma cells (LLC-PK) inhibitory concentrations (IC 50 ) of 2.8 · 10 À4 , 3.6 · 10 À4 and 2.1 · 10 À4 M, respectively, were observed.
Diarylmethyl substituted titanocenes: Promising anti-cancer drugs
Polyhedron, 2006
From the reaction of tert-butyl lithium with p-bromo-N,N-dimethylaniline (1a), p-bromoanisole (1b) or 1-bromo-3,5-dimethoxybenzene (1c), p-N,N-dimethylanilyl lithium (2a), p-anisyl lithium (2b) or (3,5-dimethoxyphenyl) lithium (2c), respectively, were obtained. When reacted with 6-(p-N,N-dimethylanilinyl)fulvene (3a), 6-(p-methoxyphenyl)fulvene (3b) or 3,5-(dimethoxyphenyl)fulvene (3c), the corresponding lithiated intermediates were formed (4a–c). Titanium tetrachloride was added “in situ”, obtaining titanocenes 5a–c, respectively. When these titanocenes were tested against pig kidney carcinoma (LLC-PK) cells, inhibitory concentrations (IC50) of 3.8 × 10−5 M, 4.5 × 10−5 M, and 7.8 × 10−5 M, respectively, were observed. These values represent improved cytotoxicity against LLC-PK, compared to their ansa-analogues.Bis-[di-(p-N,N-dimethylaminophenyl)methylcyclopentadienyl] titanium(IV) dichloride is a promising candidate for an anti-cancer drug and was synthesised starting from 6-(p-N,N-dimethylanilinyl)fulvene and 4-lithio-N,N-dimethylaniline. Herein, we present the synthesis and DFT structure of the titanocene and two further derivatives followed by MTT-based cytotoxicity tests on pig kidney carcinoma (LLC-PK) cells.
Novel benzyl substituted titanocene anti-cancer drugs
Journal of Organometallic Chemistry, 2005
From the novel reaction of Super Hydride (LiB(Et) 3 H) with 6-(p-N,N-dimethylanilinyl)fulvene (1a) or 6-(p-methoxyphenyl)fulvene (1b) the corresponding lithium cyclopentadienide intermediates (2a, 2b) were obtained. When reacted with TiCl 4 , bis-[(p-dimethylaminobenzyl)cyclopentadienyl]titanium (IV) dichloride (3a) and bis-[(p-methoxybenzyl)cyclopentadienyl]titanium (IV) dichloride (3b) were obtained. Titanocene 3a was reacted with an ethereal solution of HCl, by which its dihydrochloride derivative (3c) was formed and isolated. Titanocenes 3b and 3c were characterised by X-ray crystallography. When the titanocenes 3a-c were tested against pig kidney carcinoma (LLC-PK) cells inhibitory concentrations (IC 50 ) of 1.2 · 10 À4 M, 2.1 · 10 À5 M and 9.0 · 10 À5 M, respectively, were observed. These values represent improved cytotoxicity against LLC-PK, most notably for 3b (Titanocene Y), which is a hundred times more cytotoxic than titanocene dichloride itself.