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Studies on organometallic selective estrogen receptor modulators. (SERMs) Dual activity in the hydroxy-ferrocifen series

par Top, Siden;Vessières, Anne;Cabestaing, Claude;Laïos, Ioanna;Leclercq, Guy ;Provot, Christian;Jaouen, Gérard
Référence Journal of organometallic chemistry, 637-639, page (500-506)
Publication Publié, 2001-12

Article révisé par les pairs

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Résumé :

Synthesis of 7, a ferrocene derivative of the antiestrogenic drug hydroxytamoxifen bearing a basic chain-O(CH2)nN(CH3)2 with n=4 is presented, together with both studies of its antiproliferative effect on the hormone-dependent MCF7 cell line (estrogen receptor positive cells) and of its genotoxicity. This molecule is easily prepared via a McMurry coupling reaction. The antiproliferative effect found for 7 at an incubation molarity of 1 μM was very close to that found for the usual reference molecule, namely OH-tamoxifen. In addition to its structural antiestrogenic effect, 7 showed cytotoxic activity probably due to the vectored ferrocene. This genotoxic component was confirmed by a 3D (damaged DNA detection) test, that permits identification and quantification of lesions induced on DNA. Some key interactions of 7 docked into the alpha-estrogen receptor binding site were also shown. © 2001 Elsevier Science B.V.