Organometallic analogues of tamoxifen: Effect of the amino side-chain replacement by a carbonyl ferrocenyl moiety in hydroxytamoxifen

Since the widely prescribed selective estrogen receptor modulator (SERM) tamoxifen encounters growing cases of resistance in long-term treatments, alternative drugs with different therapeutic scopes have to be developed. Many investigators have modified the triphenylethylene scaffold, but very few have changed its amino side chain, essential for the antiestrogenic activity. For the first time, a lipophilic and stable organometallic entity, –OCH2CO-[(η5-C5H4)FeCp], has replaced this key functional side chain, while keeping a good affinity for the estrogen receptor and an antiproliferative activity on cancer cells (MCF-7 and PC-3). Its mechanism of action is likely to be different from the antihormonal pathway followed by hydroxytamoxifen, and from the cytotoxicity observed for the ferrocifens.