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Ecole Nationale Supérieure de Chimie de Paris (Chimie ParisTech), Laboratoire Charles Friedel UMR CNRS 7223, 11 rue Pierre et Marie Curie, 75231 Paris Cedex 05, France
E-mail: siden-top@chimie-paristech.fr
; Tel: +33 1 43 26 95 55
b
School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland
New J. Chem., 2011,35, 2212-2218
DOI:
10.1039/C1NJ20192A
Received
01 Mar 2011,
Accepted
12 May 2011
First published online
28 Jun 2011
We have prepared several organometallic systems whose structures are closely analogous to that of tamoxifen, the drug used in the treatment of hormone-dependent breast cancers, but which now possess two basic aminoalkyl chains: O(CH2)3NMe2. Despite the absence of a phenolic functionality, these ferrocenyl compounds 3, 4 and their organic analogue 5 recognize the estrogen receptor but in addition exhibit strong antiproliferative effects on hormone-dependent breast cancer cells (MCF-7), and also on hormone-independent ones (MDA-MB-231) with, in this case, an IC50 value of about 0.4 μM. The ferrocenyl moiety does not create a major effect here compared to a purely organic aromatic group. On the other hand, the presence within the molecule of two vicinal basic entities, potentially allowing complexation to metal ions such as Zn2+, could perhaps be the key to the antiproliferative effectiveness of this series which operates via a different mechanism to that of hydroxytamoxifen1 and hydroxyferrocifen2. The behaviour of these new species is discussed. They possess the distinctive feature of combining a strong antiproliferative effect with intense antibacterial and antifungal activity.
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