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Synthesis and biological assessment of organometallic tamoxifen derivatives for the diagnosis and the treatment of breast cancer

Anh Nguyen
Abstract : Since breast cancer is still a leading cause of cancer death among women, improvements in diagnosis and therapy for this disease have to be explored more than ever. Using robust organometallic compounds and targeting them to the estrogen receptor, enables us to broaden their applications by choosing the appropriate metal. For the first time were described compounds where the key amino side-chain of hydroxytamoxifen has been replaced by a lipophilic and stable organometallic entity, a ferrocenyl moiety. This amino side-chain was deemed essential for the anti-estrogenic activity. Additionally, the amino side-chain of the ferrocifens was also substituted by a carboxylate group. Various parameters were tested to optimise the biological activity of the ferrocenyl compounds. The versatility of some of the ferrocenyl derivatives synthetized lie in their ability to be both a potential drug and a stable precursor for the synthesis of radiopharmaceuticals. The compounds were succesfully labeled by a double ligand exchange reaction with Re and Tc, which proved to be chemioselective. These high affinity organometallic compounds could be potential site-specific radiotherapeutic (188Re derivatives), or radioimaging (99mTc derivatives) agents. Finally, in order to improve their bioavailability, two most interesting organometallic tamoxifen-like compounds were incorporated in two types of stealth nanoparticles: nanospheres and nanocapsules. An efficient anticancer organometallic triphenylethylene-loaded nanosystems have been developed for the first time. Their small size and delayed drug release, combined with their enhanced apoptotic potential, are compatible with an increased persistence in the blood and a promising antitumour activity.
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https://pastel.archives-ouvertes.fr/pastel-00003191
Contributor : Ecole Chimie Paristech <>
Submitted on : Monday, December 17, 2007 - 8:00:00 AM
Last modification on : Monday, October 19, 2020 - 11:03:46 AM
Long-term archiving on: : Wednesday, September 8, 2010 - 5:51:13 PM

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  • HAL Id : pastel-00003191, version 1

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Anh Nguyen. Synthesis and biological assessment of organometallic tamoxifen derivatives for the diagnosis and the treatment of breast cancer. Chemical Sciences. Chimie ParisTech, 2007. English. ⟨pastel-00003191⟩

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