INVITRO ESTROGENIC ACTIONS IN RAT AND HUMAN-CELLS OF HYDROXYLATED DERIVATIVES OF D16726 (ZINDOXIFENE), AN AGENT WITH KNOWN ANTIMAMMARY CANCER ACTIVITY INVIVO

  • 15 February 1988
    • journal article
    • research article
    • Vol. 48  (4) , 784-787
Abstract
A series of 2-phenyl-1-ethyl-3-methylindoles with or without a hydroxyl group in the para position of the phenyl ring and the 5 or 6 position of the indole nucleus were compared with 17.beta.-estradiol in the stimulation of (a) prolactin production in rat pituitary cells in primary culture, (b) progesterone receptor synthesis in MCF-7 cells, and (c) proliferation of MCF-7 cells. All compounds were less active than estradiol but all derivatives including D15414, the hydroxylated metabolite of D16726 (zindoxifene, a known antitumor agent against mammary cancer) were fully estrogen. Hydroxyl groups at the para position of the phenyl ring and 6 position of the indole nucleus conferred the highest estrogen potency [E50 (drug concentration producing 50% of maximum activity) in all assays around 10-10 M]. Moving or eliminating the hydroxyl on the indole ring markedly reduced the estrogen potency; however, an even more dramatic reduction in estrogenic activity was produced by removing the hydroxyl of the phenyl ring.

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