کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1322860 | 977252 | 2009 | 6 صفحه PDF | دانلود رایگان |
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.
On hormone dependent breast cancer cells, Titanocene K is highly proliferative at low concentration (0.5 μM) while Titanocene Y has almost no effect at 10 μM but exhibits a significant dose dependent cytotoxic effect when incubated with serum albumin. Ferrocene Y shows only a modest anti-proliferative effect on these cells.Figure optionsDownload as PowerPoint slide
Journal: Journal of Organometallic Chemistry - Volume 694, Issue 6, 15 March 2009, Pages 874–879