The presence of a ferrocenyl unit on an estrogenic molecule is not always sufficient to generate in vitro cytotoxicity.

We recently reported the dual (antihormonal and cytotoxic) functionality of ferrocifens, which are organometallic complexes derived from hydroxytamoxifen, the standard molecule in the treatment of hormone-dependent breast cancers. To test the hypothesis that the presence of a ferrocenyl substituent on molecules with an affinity for the estrogen receptor is sufficient to give them cytotoxic properties in vitro, we prepared complexes derived from estradiol with a ferrocenyl substituent at positions 7alpha and 17alpha. The complexes thus obtained retain a satisfactory level of affinity for the estrogen receptor (RBA values higher than 12 %).

Estradiol derivatives bearing sulfur-containing substituents at the 11beta or 7alpha positions: versatile reagents for the preparation of estrogen conjugates.

Estradiol derivatives bearing HS-, HSCH(2)-, HSCH(2)CH(2)-, MeS-, MeSCH(2)-, MeSCH(2)CH(2)-, or PhCH(2)SCH(2)CH(2)-groups at the 11beta position or an HS-group at the 7alpha position have been synthesized, and their binding affinity to the estrogen receptor (ER) determined. Nearly all of these substituted estrogens retain high binding affinity, and at the 11beta position, the sulfur atom has an effect on ER binding that is similar to that of a carbon atom. These thiol derivatives are promising intermediates for the preparation of a variety of estradiol conjugates.