Proliferative and anti-proliferative effects of titanium- and iron-based metallocene anti-cancer drugs |
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Authors: | Anne Vessières Marie-Aude Plamont James Claffey Megan Hogan Katja Strohfeldt |
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Institution: | a Laboratoire de Chimie et Biochimie des Complexes Moléculaires, École Nationale Supérieure de Chimie de Paris, UMR CNRS 7576, 11, rue Pierre et Marie Curie, 75231 Paris 05, France b Conway Institute of Biomolecular and Biomedical Research, Centre for Synthesis and Chemical Biology, UCD School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland |
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Abstract: | In previous work we have found that Cp2TiCl2 and its corresponding derivative of tamoxifen, Titanocene tamoxifen, show an unexpected proliferative effect on hormone dependent breast cancer cells MCF-7. In order to check if this behavior is a general trend for titanocene derivatives we have tested two other titanocene derivatives, Titanocene Y and Titanocene K, on this cell line. Interestingly, these two titanocene complexes behave in a totally different manner. Titanocene K is highly proliferative on MCF-7 cells even at low concentrations (0.5 μM), thus behave almost similarly to Cp2TiCl2. This proliferative effect is also observed in the presence of bovine serum albumin (BSA). In contrast, Titanocene Y alone has almost no effect on MCF-7 at a concentration of 10 μM, but exhibits a significant dose dependent cytotoxic effect of up to 50% when incubated with BSA (20-50 μg/mL). This confirms the crucial role played by the binding to serum proteins in the expression of the in vivo, cytotoxicity of the titanocene complexes. From the hydridolithiation reaction of 6-p-anisylfulvene with LiBEt3H followed by transmetallation with iron dichloride bis-(p-methoxy-benzyl)cyclopentadienyl]iron(II)] (Ferrocene Y) was synthesised. This complex, which was characterised by single crystal X-ray diffraction, contains the robust ferrocenyl unit instead of Ti associated with easily leaving groups such as chlorine and shows only a modest cytotoxicity against MCF-7 or MDA-MB-231 cells. |
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Keywords: | Bioorganometallic chemistry Anti-cancer drugs Cisplatin Titanocene Ferrocene Breast cancer |
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