We report here the synthesis and the strong and unexpected antiproliferative effect of the organometallic diphenolic compound 1,1-bis(4'-hydroxyphenyl)-2-ferrocenyl-but-1-ene (4) on both hormone-dependent (MCF7) and -independent (MDA-MB231) breast cancer cells (IC(50) = 0.7 and 0.6 microM). Surprisingly, 6 [1,2-bis(4'-hydroxyphenyl)-2-ferrocenyl-but-1-ene], the regioisomer of 4, shows only a modest effect on these cell lines. This pertinent organometallic modification seems to trigger an intracellular oxidation of the structurally favorable compound 4, leading to the generation of a potent cytotoxic compound.

Depending on the presence or absence of the estrogen receptor in the cells, breast cancer today is often treated by endocrine therapy (tamoxifen) or chemotherapy, respectively. We present now a new paradigm for breast cancer treatment, taking advantage of concepts in bioorganometallic chemistry. In this way, we have synthesized molecules containing an organometallic moiety (ferrocene), and a biovector (hydroxytamoxifen), yielding compounds which display a new therapeutic spectrum consisting of antiestrogenicity and cytotoxicity. A structure–activity relationship study has shown that a ferrocene group, linked to a para-phenol group by a conjugated spacer, is a necessary motif for strong cytotoxic effects to be observed.