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Ferrocenyl Quinone Methide–Thiol Adducts as New Antiproliferative Agents: Synthesis, Metabolic Formation from Ferrociphenols, and Oxidative Transformation
Author(s) -
Wang Yong,
Richard MarieAude,
Top Siden,
Dansette Patrick M.,
Pigeon Pascal,
Vessières Anne,
Mansuy Daniel,
Jaouen Gérard
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201603931
Subject(s) - quinone methide , chemistry , nucleophile , electrophile , reactivity (psychology) , quinone , moiety , oxidizing agent , adduct , thiol , redox , combinatorial chemistry , oxidative phosphorylation , stereochemistry , organic chemistry , biochemistry , catalysis , alternative medicine , pathology , medicine
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.