Book of Abstracts - Ruhr-Universität Bochum

OP-9
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Synthesis and Structure-Activity Relationship of Organometallic Derivatives
of Curcumin as Anticancer Agents
Anusch Arezki, Emilie Brulé,* and Gérard Jaouen
Chimie ParisTech (ENSCP), Laboratoire Charles Friedel (UMR 7223),
Organometallic Medicinal Chemistry Group
11 rue Pierre et Marie Curie, 75231 Paris Cedex 05, France
E-mail: anusch-arezki@chimie-paristech.fr
Turmeric and especially its main and active constituent curcumin have traditionally been used as a
food preservative, as well as a natural remedy in Ayurvedic and Chinese medicine for centuries. But it
is only within the past few years that modern research has focused on curcumin's biological properties
(antioxidant, anti-inflammatory...) and in particular on the extraordinary actions of curcumin in
preventing and fighting cancer. Curcumin has at least a dozen separate ways of interfering with cancer
progression, but at the same time preserving normal cells. 1
In our laboratory, we chose different curcuminoids as starting materials to lead to a novel class of
bioorganometallic anticancer agents by covalently grafting different organometallic ligands to the
curcuminoid skeleton. The synthesis of the new ferrocenyl molecules was primarily done by
substitution of the central carbon of the curcuminoids, 2 which has shown to have a crucial influence on
activity against some cancer cells. 3 The new complexes were tested in vitro on different cancer cell
lines, such as prostate and skin (melanoma), and showed promising cytotoxic effects on all types. For
some of the ferrocenyl-curcuminoid derivatives, enhanced cytotoxic activity was observed compared
to the organic curcuminoid analogues, with up to a 3- and 4-fold improvement on prostate and
melanoma cells, respectively.
MeO
HO
OH O
Curcumin
OMe
OH
25
MeO
R 1
OH O
R 2 R 2
R 1 : H, OH, OMe
R 2 : H, OMe
= organic linker
Curcumin and ferrocenyl derivatives of several curcuminoids
Due to encouraging results in vitro, the National Institute of Health of the United States is currently
screening, in collaboration with the National Cancer Institute, one selected ferrocenyl curcuminoid on
60 different cancer cell lines (colon, lung, central nervous system,…). Primary single dose testing
revealed a particular selectivity of the compound for certain types of cancer in vitro, which has led to
more detailed investigations, presently ongoing.
Acknowledgement to the Gottlieb-Daimler and Carl-Benz Foundation (Germany) and the Association
pour la Recherche sur le Cancer (ARC) (France) for PhD funding.
References
1. A. Goel, A. B. Kunnumakkara, B. B. Aggarwal, Biochem. Pharmacol. 2008, 75, 787-809.
2. A. Arezki, E. Brulé, G. Jaouen, Organometallics 2009, 28, 1606-1609.
3. L. Lin, Q. Shi, A. K. Nyarko, K. F. Bastow et al. J. Med. Chem. 2006, 49, 3963-3972.
4. P. Anand, A. B. Kunnumakkara, R. A. Newman, B. B. Aggarwal, Mol. Pharm. 2007, 4, 804-818.
Fe
OMe
R 1