Synthesis and cytotoxicity studies of methoxy benzyl substituted titanocenes |
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Authors: | James Claffey |
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Institution: | Conway Institute of Biomolecular and Biomedical Research, The UCD School of Chemistry and Chemical Biology, Centre for Synthesis and Chemical Biology (CSCB), University College Dublin, Belfield, Dublin 4, Ireland |
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Abstract: | From the reaction of 6(2-methoxy-phenyl)fulvene (1a), 6(3-methoxy-phenyl)fulvene (1b), 6(3,4-dimethoxy-phenyl)fulvene (1c) and 6(3,4,5-trimethoxy-phenyl)fulvene (1d) with LiBEt3H, lithiated cyclopentadienide intermediates 2a-d were synthesised. These intermediates were then transmetallated to titanium with TiCl4 to give benzyl substituted titanocenes bis-(2-methoxy-benzyl)cyclopentadienyl]titanium(IV) dichloride (3a), bis-(3-methoxy-benzyl)cyclopentadienyl]titanium(IV) dichloride (3b), bis-(3,4-dimethoxy-benzyl)cyclopentadienyl]titanium(IV) dichloride (3c) and bis-(3,4,5-trimethoxy-benzyl)cyclopentadienyl]titanium(IV) dichloride (3d). The three titanocenes 3a-c were characterised by single crystal X-ray diffraction, while the structure of the fourth titanocene 3d was elucidated through a DFT calculation. All four titanocenes had their cytotoxicity investigated through preliminary in vitro testing on the LLC-PK (pig kidney epithelial) cell line in order to determine their IC50 values. Titanocenes 3a-d were found to have IC50 values of 97, 159, 88 and 253 μM, respectively. All four titanocene derivatives show significant cytotoxicity improvement when compared to unsubstituted titanocene dichloride. |
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Keywords: | Anti-cancer drugs Cisplatin Titanocene Hydridolithiation Fulvene RCC LLC-PK |
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