Two 11ß-derivatives of estradiol (E2) were tested for their potential antiestrogenic activity in the MCF-7 breast cancer model: one contained a phenoxydimethylaminoethyl side-chain (RU 39 411 or RU 39,411), the other a pentafluoropentylsulfinyl side-chain (RU 58 668 or RU 58,668). The former compound displayed mixed estrogenic/antiestrogenic properties, while the latter indicated only an antiestrogenic activity. Both the compounds produced a growth inhibition of MCF-7 at doses related to their binding affinity for the estrogen receptor (ER); E2 suppressed this inhibition. The compounds also down-regulated the estrogen binding capacity of the cells but failed to reduce ER mRNA levels, indicating that the grafting of their side-chains prevented this antagonistic effect usually observed with steroidal estrogens. Assessment of ER levels by enzyme immunoassay revealed a marked increase with RU 39 411 and a decrease with RU 58 668; different mechanisms of action should, therefore, be considered. Finally, the estrogenic activity of RU 39 411 was demonstrated by its strong ability to induce synthesis of the progesterone receptor; RU 58 668 failed to display this agonistic activity.
