Ferrocenyl Quinone Methide-Thiol Adducts as New Antiproliferative Agents: Synthesis, Metabolic Formation from Ferrociphenols, and Oxidative Transformation
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- 作者：Dr. Yong Wang ; Dr. Marie-Aude Richard ; Dr. Siden Top ; Dr. Patrick M. Dansette ; Dr. Pascal Pigeon ; Dr. Anne Vessiè ; res ; Dr. Daniel Mansuy and Prof. Gé ; rard Jaouen
- 刊名：Angewandte Chemie
- 出版年：2016
- 出版时间：August 22, 2016
- 年：2016
- 卷：128
- 期：35
- 页码：10587-10590
- 全文大小：795K
- ISSN：1521-3757
文摘
Ferrociphenols (FCs) and their oxidized, electrophilic quinone methide metabolites (FC-QMs) are organometallic compounds related to tamoxifen that exhibit strong antiproliferative properties. To evaluate the reactivity of FC-QMs toward cellular nucleophiles, we studied their reaction with selected thiols. A series of new compounds resulting from the addition of these nucleophiles, the FC-SR adducts, were thus synthesized and completely characterized. Such conjugates are formed upon metabolism of FCs by liver microsomes in the presence of NADPH and thiols. Some of the FC-SR adducts exhibit antiproliferative properties comparable to those of their FC precursors. Under oxidizing conditions they either revert to their FC-QM precursors or transform into new quinone methides (QMs) containing the SR moiety, FC-SR-QM. These results provide interesting data about the reactivity and mechanism of antiproliferative effects of FCs, and also open the way to a new series of organometallic antitumor compounds.