Book of Abstracts - Ruhr-Universität Bochum

P-23
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Antiproliferative Activity of Diphenylmethylidenyl-[3]ferrocenophanes on Breast
and Prostate Hormone-independent Cancer Cell Lines
Meral Gormen, a Pascal Pigeon, a Siden Top,* a Elizabeth A. Hillard, a Marie-Aude Plamont, a
Anne Vessières, a amd Gérard Jaouen a
a ENSCP, Laboratoire Charles Friedel, UMR 7223, 11, Rue Pierre et Marie Curie, 75231, Paris,
Cedex 05, France. E-mail: meral-gormen@chimie-paristech.fr
Breast cancer is the leading cause of cancer death among women in the Western world and accounts for
23% of all female cancer cases worldwide. 1 In terms of incidence rate, breast cancer touches one woman in
eight in Western countries.
Tamoxifen, whose active metabolite is hydroxytamoxifen (1), is currently the most widely used antiestrogen
in the adjuvant therapy of hormone-dependent breast cancers. 2 However, it is known that one-third of these
cases are hormone-independent cancers, and don’t respond to tamoxifen therapy. We found that
hydroxyferrocifen (2) and ferrocifenol (3) exhibit strong antiproliferative activities against both hormonedependent
MCF-7 cancer cells and hormone-independent MDA-MB-231cancer cells. 3
OH
OH
Fe
Fe
Fe
O(CH2) 2N(CH3) 2
OR
1 2. R = (CH2) 3N(CH3) 2
3. R = H
4 5
R1,R2= H,OH,NH2,NHAc It has recently been shown that dihydroxy [3]ferrocenophane 4 is 7 times more potent than ferrocifenol 3 on
MDA-MB-231 cells. 4 We now extend our work on this new and interesting series by synthesizing other
compounds by varying the nature of the substituents R1 and R2 (5). 5 These new compounds show high
activity compared to that of classical ferrocene analogues. The inhibitory concentrations (IC50) of 5 on
MDA-MB-231 cells range from 50 to 90 nM.
Our work was extended to prostate cancer which is one of the most frequently diagnosed cancers and is the
second leading cause of cancer death in men after lung. We found that [3]ferrocenophane derivatives are also
active against PC3 hormone-independent prostate cancer cells with IC50 ranging from 20 to 140 nM.
Synthesis and antitumor activities of [3]ferrocenophane derivatives will be presented.
References
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Prevalence Worldwide. IARC CancerBase No. 5 version 20. IARCPress, Lyon, France, 2004. (b) A.
Jemal, R. Siegel, E. Ward, T. Murray, J. Xu, M. J. Thun, CA Cancer J Clin 2007, 57, 43-66. (c) R. Y.
Wood, N.R. Della-Monica. Int. J. Older People Nursing, 2006, 1 (2), 75-84.
2. (a) V. C. Jordan, J. Med. Chem., 2003, 46 (6), 883-908 (b) V. C. Jordan, J. Med. Chem., 2003, 46 (7),
1081-1111.
3. S. Top, A. Vessières, G. Leclercq, J. Quivy, J. Tang, J. Vaissermann, M. Huche, G. Jaouen.
Chem. Eur. J., 2003, 9, 5223-5236. (b) A. Vessières, S. Top, P. Pigeon, E. Hillard, L. Boubeker,
D. Spera, G. Jaouen J. Med. Chem., 2005, 48, 3937-3940
4. D. Plazuk, A. Vessieres, E.A. Hillard, et al. J. Med. Chem., 2009, 52, 4964-4967.
5. M. Gormen, P. Pigeon, E.A. Hillard, et al. Tetrahedron Lett., 2010, 51, 118-120.
81
HO
OH
R 1
R 2