We recently reported the dual (antihormonal and cytotoxic) functionality of ferrocifens, which are organometallic complexes derived from hydroxytamoxifen, the std. mol. in the treatment of hormone-dependent breast cancers. To test the hypothesis that the presence of a ferrocenyl substituent on mols. with an affinity for the estrogen receptor is sufficient to give them cytotoxic properties in vitro, we prepd. complexes derived from estradiol with a ferrocenyl substituent at positions 7α and 17α. The complexes thus obtained retain a satisfactory level of affinity for the estrogen receptor (RBA values higher than 12 %). At low concns. (0.1-1 μM) the complexes show an estrogenic effect in vitro equiv. to that of estradiol on hormone-dependent (MCF-7) breast cancer cells, and no cytotoxic effect on hormone-independent (MDA-MB-231) breast cancer cells. At high concns. (up to 50 μM) the 17α-ethynylferrocenyl estradiol and 7α-ferrocenylmethylthio estradiol become cytotoxic (IC50 = 13.2 μM and 18.8 μM, resp.) while the 17α-ferrocenylestradiol remains non toxic. The low toxicity of these compds. support our hypothesis that electronic communication between the ferrocenyl and phenol moieties in the hydroxyferrocifens series is a key parameter in the generation of cytotoxic effects at submicromolar concns.
The presence of a ferrocenyl unit on an estrogenic molecule is not always sufficient to generate in vitro cytotoxicity
FIASCHI, RITA;
2006-01-01
Abstract
We recently reported the dual (antihormonal and cytotoxic) functionality of ferrocifens, which are organometallic complexes derived from hydroxytamoxifen, the std. mol. in the treatment of hormone-dependent breast cancers. To test the hypothesis that the presence of a ferrocenyl substituent on mols. with an affinity for the estrogen receptor is sufficient to give them cytotoxic properties in vitro, we prepd. complexes derived from estradiol with a ferrocenyl substituent at positions 7α and 17α. The complexes thus obtained retain a satisfactory level of affinity for the estrogen receptor (RBA values higher than 12 %). At low concns. (0.1-1 μM) the complexes show an estrogenic effect in vitro equiv. to that of estradiol on hormone-dependent (MCF-7) breast cancer cells, and no cytotoxic effect on hormone-independent (MDA-MB-231) breast cancer cells. At high concns. (up to 50 μM) the 17α-ethynylferrocenyl estradiol and 7α-ferrocenylmethylthio estradiol become cytotoxic (IC50 = 13.2 μM and 18.8 μM, resp.) while the 17α-ferrocenylestradiol remains non toxic. The low toxicity of these compds. support our hypothesis that electronic communication between the ferrocenyl and phenol moieties in the hydroxyferrocifens series is a key parameter in the generation of cytotoxic effects at submicromolar concns.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
