The Experts below are selected from a list of 22164 Experts worldwide ranked by ideXlab platform
Matthias Tacke - One of the best experts on this subject based on the ideXlab platform.
-
diarylmethyl substituted titanocenes promising anti cancer drugs
Polyhedron, 2006Co-Authors: Clara Pampillón, Katja Strohfeldt, Nigel J. Sweeney, Oscar Mendoza, Matthias TackeAbstract:Abstract 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.
-
novel benzyl substituted titanocene anti cancer drugs
Journal of Organometallic Chemistry, 2005Co-Authors: Nigel J. Sweeney, Katja Strohfeldt, Clara Pampillón, Franzjosef K Rehmann, Helge Mullerbunz, Oscar Mendoza, Matthias TackeAbstract:From the novel reaction of Super Hydride (LiB(Et)3H) 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 TiCl4, 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 (IC50) of 1.2 · 10 � 4 M, 2.1 · 10 � 5 M and 9.0 · 10 � 5 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. � 2005 Elsevier B.V. All rights reserved.
-
heteroaryl substituted ansa titanocene anti cancer drugs derived from fulvenes and titanium dichloride
Applied Organometallic Chemistry, 2005Co-Authors: Franzjosef K Rehmann, Katja Strohfeldt, Nigel J. Sweeney, Laurence P Cuffe, William M Gallagher, Oscar Mendoza, Dilip K Rai, Matthias TackeAbstract: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.
-
methoxy phenyl substituted ansa titanocenes as potential anti cancer drugs derived from fulvenes and titanium dichloride
Journal of Inorganic Biochemistry, 2004Co-Authors: Matthias Tacke, Franzjosef K Rehmann, Laurence P Cuffe, Helge Mullerbunz, William M Gallagher, Oscar Mendoza, Ying Lou, Nigel J. SweeneyAbstract:Starting from 6-(4'-methoxyphenyl)fulvene (1a), 6-(2',4',6'-trimethoxyphenyl)fulvene (1b), or 6-(3',5'-dimethoxyphenyl)fulvene (1c), [1,2-di(cyclopentadienyl)-1,2-di(4'-methoxyphenyl)-ethanediyl] titanium dichloride (2a), [1,2-di(cyclopentadienyl)-1,2-bis(2',4',6'-trimethoxyphenyl)-ethanediyl] titanium dichloride (2b), and [1,2-di(cyclopentadienyl)-1,2-bis(3',5'-dimethoxyphenyl)-ethanediyl] titanium dichloride (2c) were synthesised. When titanocenes 2a-c were tested against pig Kidney Carcinoma cells (LLC-PK) inhibitory concentrations (IC50) of 2.8 x 10(-4), 3.6 x 10(-4) and 2.1 x 10(-4) M, respectively, were observed.
-
novel titanocene anti cancer drugs derived from fulvenes and titanium dichloride
Journal of Organometallic Chemistry, 2004Co-Authors: Matthias Tacke, Franzjosef K Rehmann, Lorcan T Allen, Laurence P Cuffe, Helge Mullerbunz, William M Gallagher, Oscar Mendoza, Nigel J. SweeneyAbstract:AbstractStarting from 6-(p N;N-dimethylanilinyl)fulvene (1a) or 6-(pentamethylphenyl)fulvene (1b) [1,2-di(cyclopentadienyl)-1,2-di(p N;N-dimethylaminophenyl)ethanediyl] titanium dichloride (2a) and [1,2-di(cyclopentadienyl)-1,2-bis(pentamethylphe-nyl)ethanediyl] titanium dichloride (2b) and their corresponding dithiocyanato complexes (3a, 3b) were synthesized. Titanocene 2bdid not show a cytotoxic effect, but when 2a was tested against pig Kidney Carcinoma cells (LLC-PK) or human ovarian Carcinomacells (A2780/cp70) inhibitory concentrations (IC 50 ) of 2.7 10 4 and 1.9 10 4 M, respectively, were observed. 2004 Elsevier B.V. All rights reserved. Keywords: Anti-cancer drug; cis-Platinum; Titanocene; Fulvene; LLC-PK; A2780/cp70 1. IntroductionDespite the resounding success of cis-platinum andclosely related platinum anti-tumor agents, the move-ment of other transition-metal anti-cancer drugs to-wards the clinic has been exceptionally slow [1–3].Metallocene dichlorides (Cp 2 MCl 2 )withM¼Ti, V, Nband Mo show remarkable anti-tumor activity [4,5].However, only titanocene dichloride has reached Phase Iclinical trials so far, with a maximum tolerable dose of315 mg/m
Nigel J. Sweeney - One of the best experts on this subject based on the ideXlab platform.
-
diarylmethyl substituted titanocenes promising anti cancer drugs
Polyhedron, 2006Co-Authors: Clara Pampillón, Katja Strohfeldt, Nigel J. Sweeney, Oscar Mendoza, Matthias TackeAbstract:Abstract 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.
-
novel benzyl substituted titanocene anti cancer drugs
Journal of Organometallic Chemistry, 2005Co-Authors: Nigel J. Sweeney, Katja Strohfeldt, Clara Pampillón, Franzjosef K Rehmann, Helge Mullerbunz, Oscar Mendoza, Matthias TackeAbstract:From the novel reaction of Super Hydride (LiB(Et)3H) 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 TiCl4, 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 (IC50) of 1.2 · 10 � 4 M, 2.1 · 10 � 5 M and 9.0 · 10 � 5 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. � 2005 Elsevier B.V. All rights reserved.
-
heteroaryl substituted ansa titanocene anti cancer drugs derived from fulvenes and titanium dichloride
Applied Organometallic Chemistry, 2005Co-Authors: Franzjosef K Rehmann, Katja Strohfeldt, Nigel J. Sweeney, Laurence P Cuffe, William M Gallagher, Oscar Mendoza, Dilip K Rai, Matthias TackeAbstract: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.
-
methoxy phenyl substituted ansa titanocenes as potential anti cancer drugs derived from fulvenes and titanium dichloride
Journal of Inorganic Biochemistry, 2004Co-Authors: Matthias Tacke, Franzjosef K Rehmann, Laurence P Cuffe, Helge Mullerbunz, William M Gallagher, Oscar Mendoza, Ying Lou, Nigel J. SweeneyAbstract:Starting from 6-(4'-methoxyphenyl)fulvene (1a), 6-(2',4',6'-trimethoxyphenyl)fulvene (1b), or 6-(3',5'-dimethoxyphenyl)fulvene (1c), [1,2-di(cyclopentadienyl)-1,2-di(4'-methoxyphenyl)-ethanediyl] titanium dichloride (2a), [1,2-di(cyclopentadienyl)-1,2-bis(2',4',6'-trimethoxyphenyl)-ethanediyl] titanium dichloride (2b), and [1,2-di(cyclopentadienyl)-1,2-bis(3',5'-dimethoxyphenyl)-ethanediyl] titanium dichloride (2c) were synthesised. When titanocenes 2a-c were tested against pig Kidney Carcinoma cells (LLC-PK) inhibitory concentrations (IC50) of 2.8 x 10(-4), 3.6 x 10(-4) and 2.1 x 10(-4) M, respectively, were observed.
-
novel titanocene anti cancer drugs derived from fulvenes and titanium dichloride
Journal of Organometallic Chemistry, 2004Co-Authors: Matthias Tacke, Franzjosef K Rehmann, Lorcan T Allen, Laurence P Cuffe, Helge Mullerbunz, William M Gallagher, Oscar Mendoza, Nigel J. SweeneyAbstract:AbstractStarting from 6-(p N;N-dimethylanilinyl)fulvene (1a) or 6-(pentamethylphenyl)fulvene (1b) [1,2-di(cyclopentadienyl)-1,2-di(p N;N-dimethylaminophenyl)ethanediyl] titanium dichloride (2a) and [1,2-di(cyclopentadienyl)-1,2-bis(pentamethylphe-nyl)ethanediyl] titanium dichloride (2b) and their corresponding dithiocyanato complexes (3a, 3b) were synthesized. Titanocene 2bdid not show a cytotoxic effect, but when 2a was tested against pig Kidney Carcinoma cells (LLC-PK) or human ovarian Carcinomacells (A2780/cp70) inhibitory concentrations (IC 50 ) of 2.7 10 4 and 1.9 10 4 M, respectively, were observed. 2004 Elsevier B.V. All rights reserved. Keywords: Anti-cancer drug; cis-Platinum; Titanocene; Fulvene; LLC-PK; A2780/cp70 1. IntroductionDespite the resounding success of cis-platinum andclosely related platinum anti-tumor agents, the move-ment of other transition-metal anti-cancer drugs to-wards the clinic has been exceptionally slow [1–3].Metallocene dichlorides (Cp 2 MCl 2 )withM¼Ti, V, Nband Mo show remarkable anti-tumor activity [4,5].However, only titanocene dichloride has reached Phase Iclinical trials so far, with a maximum tolerable dose of315 mg/m
Oscar Mendoza - One of the best experts on this subject based on the ideXlab platform.
-
diarylmethyl substituted titanocenes promising anti cancer drugs
Polyhedron, 2006Co-Authors: Clara Pampillón, Katja Strohfeldt, Nigel J. Sweeney, Oscar Mendoza, Matthias TackeAbstract:Abstract 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.
-
novel benzyl substituted titanocene anti cancer drugs
Journal of Organometallic Chemistry, 2005Co-Authors: Nigel J. Sweeney, Katja Strohfeldt, Clara Pampillón, Franzjosef K Rehmann, Helge Mullerbunz, Oscar Mendoza, Matthias TackeAbstract:From the novel reaction of Super Hydride (LiB(Et)3H) 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 TiCl4, 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 (IC50) of 1.2 · 10 � 4 M, 2.1 · 10 � 5 M and 9.0 · 10 � 5 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. � 2005 Elsevier B.V. All rights reserved.
-
heteroaryl substituted ansa titanocene anti cancer drugs derived from fulvenes and titanium dichloride
Applied Organometallic Chemistry, 2005Co-Authors: Franzjosef K Rehmann, Katja Strohfeldt, Nigel J. Sweeney, Laurence P Cuffe, William M Gallagher, Oscar Mendoza, Dilip K Rai, Matthias TackeAbstract: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.
-
methoxy phenyl substituted ansa titanocenes as potential anti cancer drugs derived from fulvenes and titanium dichloride
Journal of Inorganic Biochemistry, 2004Co-Authors: Matthias Tacke, Franzjosef K Rehmann, Laurence P Cuffe, Helge Mullerbunz, William M Gallagher, Oscar Mendoza, Ying Lou, Nigel J. SweeneyAbstract:Starting from 6-(4'-methoxyphenyl)fulvene (1a), 6-(2',4',6'-trimethoxyphenyl)fulvene (1b), or 6-(3',5'-dimethoxyphenyl)fulvene (1c), [1,2-di(cyclopentadienyl)-1,2-di(4'-methoxyphenyl)-ethanediyl] titanium dichloride (2a), [1,2-di(cyclopentadienyl)-1,2-bis(2',4',6'-trimethoxyphenyl)-ethanediyl] titanium dichloride (2b), and [1,2-di(cyclopentadienyl)-1,2-bis(3',5'-dimethoxyphenyl)-ethanediyl] titanium dichloride (2c) were synthesised. When titanocenes 2a-c were tested against pig Kidney Carcinoma cells (LLC-PK) inhibitory concentrations (IC50) of 2.8 x 10(-4), 3.6 x 10(-4) and 2.1 x 10(-4) M, respectively, were observed.
-
novel titanocene anti cancer drugs derived from fulvenes and titanium dichloride
Journal of Organometallic Chemistry, 2004Co-Authors: Matthias Tacke, Franzjosef K Rehmann, Lorcan T Allen, Laurence P Cuffe, Helge Mullerbunz, William M Gallagher, Oscar Mendoza, Nigel J. SweeneyAbstract:AbstractStarting from 6-(p N;N-dimethylanilinyl)fulvene (1a) or 6-(pentamethylphenyl)fulvene (1b) [1,2-di(cyclopentadienyl)-1,2-di(p N;N-dimethylaminophenyl)ethanediyl] titanium dichloride (2a) and [1,2-di(cyclopentadienyl)-1,2-bis(pentamethylphe-nyl)ethanediyl] titanium dichloride (2b) and their corresponding dithiocyanato complexes (3a, 3b) were synthesized. Titanocene 2bdid not show a cytotoxic effect, but when 2a was tested against pig Kidney Carcinoma cells (LLC-PK) or human ovarian Carcinomacells (A2780/cp70) inhibitory concentrations (IC 50 ) of 2.7 10 4 and 1.9 10 4 M, respectively, were observed. 2004 Elsevier B.V. All rights reserved. Keywords: Anti-cancer drug; cis-Platinum; Titanocene; Fulvene; LLC-PK; A2780/cp70 1. IntroductionDespite the resounding success of cis-platinum andclosely related platinum anti-tumor agents, the move-ment of other transition-metal anti-cancer drugs to-wards the clinic has been exceptionally slow [1–3].Metallocene dichlorides (Cp 2 MCl 2 )withM¼Ti, V, Nband Mo show remarkable anti-tumor activity [4,5].However, only titanocene dichloride has reached Phase Iclinical trials so far, with a maximum tolerable dose of315 mg/m
Franzjosef K Rehmann - One of the best experts on this subject based on the ideXlab platform.
-
novel benzyl substituted titanocene anti cancer drugs
Journal of Organometallic Chemistry, 2005Co-Authors: Nigel J. Sweeney, Katja Strohfeldt, Clara Pampillón, Franzjosef K Rehmann, Helge Mullerbunz, Oscar Mendoza, Matthias TackeAbstract:From the novel reaction of Super Hydride (LiB(Et)3H) 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 TiCl4, 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 (IC50) of 1.2 · 10 � 4 M, 2.1 · 10 � 5 M and 9.0 · 10 � 5 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. � 2005 Elsevier B.V. All rights reserved.
-
heteroaryl substituted ansa titanocene anti cancer drugs derived from fulvenes and titanium dichloride
Applied Organometallic Chemistry, 2005Co-Authors: Franzjosef K Rehmann, Katja Strohfeldt, Nigel J. Sweeney, Laurence P Cuffe, William M Gallagher, Oscar Mendoza, Dilip K Rai, Matthias TackeAbstract: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.
-
methoxy phenyl substituted ansa titanocenes as potential anti cancer drugs derived from fulvenes and titanium dichloride
Journal of Inorganic Biochemistry, 2004Co-Authors: Matthias Tacke, Franzjosef K Rehmann, Laurence P Cuffe, Helge Mullerbunz, William M Gallagher, Oscar Mendoza, Ying Lou, Nigel J. SweeneyAbstract:Starting from 6-(4'-methoxyphenyl)fulvene (1a), 6-(2',4',6'-trimethoxyphenyl)fulvene (1b), or 6-(3',5'-dimethoxyphenyl)fulvene (1c), [1,2-di(cyclopentadienyl)-1,2-di(4'-methoxyphenyl)-ethanediyl] titanium dichloride (2a), [1,2-di(cyclopentadienyl)-1,2-bis(2',4',6'-trimethoxyphenyl)-ethanediyl] titanium dichloride (2b), and [1,2-di(cyclopentadienyl)-1,2-bis(3',5'-dimethoxyphenyl)-ethanediyl] titanium dichloride (2c) were synthesised. When titanocenes 2a-c were tested against pig Kidney Carcinoma cells (LLC-PK) inhibitory concentrations (IC50) of 2.8 x 10(-4), 3.6 x 10(-4) and 2.1 x 10(-4) M, respectively, were observed.
-
novel titanocene anti cancer drugs derived from fulvenes and titanium dichloride
Journal of Organometallic Chemistry, 2004Co-Authors: Matthias Tacke, Franzjosef K Rehmann, Lorcan T Allen, Laurence P Cuffe, Helge Mullerbunz, William M Gallagher, Oscar Mendoza, Nigel J. SweeneyAbstract:AbstractStarting from 6-(p N;N-dimethylanilinyl)fulvene (1a) or 6-(pentamethylphenyl)fulvene (1b) [1,2-di(cyclopentadienyl)-1,2-di(p N;N-dimethylaminophenyl)ethanediyl] titanium dichloride (2a) and [1,2-di(cyclopentadienyl)-1,2-bis(pentamethylphe-nyl)ethanediyl] titanium dichloride (2b) and their corresponding dithiocyanato complexes (3a, 3b) were synthesized. Titanocene 2bdid not show a cytotoxic effect, but when 2a was tested against pig Kidney Carcinoma cells (LLC-PK) or human ovarian Carcinomacells (A2780/cp70) inhibitory concentrations (IC 50 ) of 2.7 10 4 and 1.9 10 4 M, respectively, were observed. 2004 Elsevier B.V. All rights reserved. Keywords: Anti-cancer drug; cis-Platinum; Titanocene; Fulvene; LLC-PK; A2780/cp70 1. IntroductionDespite the resounding success of cis-platinum andclosely related platinum anti-tumor agents, the move-ment of other transition-metal anti-cancer drugs to-wards the clinic has been exceptionally slow [1–3].Metallocene dichlorides (Cp 2 MCl 2 )withM¼Ti, V, Nband Mo show remarkable anti-tumor activity [4,5].However, only titanocene dichloride has reached Phase Iclinical trials so far, with a maximum tolerable dose of315 mg/m
Katja Strohfeldt - One of the best experts on this subject based on the ideXlab platform.
-
diarylmethyl substituted titanocenes promising anti cancer drugs
Polyhedron, 2006Co-Authors: Clara Pampillón, Katja Strohfeldt, Nigel J. Sweeney, Oscar Mendoza, Matthias TackeAbstract:Abstract 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.
-
novel benzyl substituted titanocene anti cancer drugs
Journal of Organometallic Chemistry, 2005Co-Authors: Nigel J. Sweeney, Katja Strohfeldt, Clara Pampillón, Franzjosef K Rehmann, Helge Mullerbunz, Oscar Mendoza, Matthias TackeAbstract:From the novel reaction of Super Hydride (LiB(Et)3H) 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 TiCl4, 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 (IC50) of 1.2 · 10 � 4 M, 2.1 · 10 � 5 M and 9.0 · 10 � 5 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. � 2005 Elsevier B.V. All rights reserved.
-
heteroaryl substituted ansa titanocene anti cancer drugs derived from fulvenes and titanium dichloride
Applied Organometallic Chemistry, 2005Co-Authors: Franzjosef K Rehmann, Katja Strohfeldt, Nigel J. Sweeney, Laurence P Cuffe, William M Gallagher, Oscar Mendoza, Dilip K Rai, Matthias TackeAbstract: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.
