Acetoxy-substituted 1,1,2-triphenylbut-1-enes with antiestrogenic and mammary tumor inhibiting properties.
1,1,2-Triphenylbut-1-enes (E- and Z-10-12), which are substituted with one p- and one m-acetoxy group in two different aromatic rings, were synthesized. The E and Z isomers were isolated, and their identity was established by 1H NMR spectroscopy. A study of the structure-activity relationship was carried out with regard to estradiol receptor affinity in vitro, estrogenic and antiestrogenic properties (mouse), inhibition of the hormone-dependent human MCF7 breast cancer cell line in vitro, and the hormone-dependent MXT mammary tumor of the mouse in vivo. Among the tested compounds, (E)- and (Z)-1-(3-acetoxyphenyl)-1-(4-acetoxyphenyl)-2-phenylbut-1-enes+  ++ (E-10 and Z-10) and (Z)-1-(3-acetoxyphenyl)-1-phenyl-2-(4-acetoxyphenyl)-but-1-ene (Z-12) proved to be partial antiestrogens, which lead to an inhibition of the MCF7 cell line. They exert a growth-inhibiting activity on the hormone-dependent MXT mammary carcinoma of the mouse. In the case of E-10 and Z-10, this effect is only slightly weaker than that of 1,1-bis(4-acetoxyphenyl)-2-phenylbut-1-ene (13) and tamoxifen. Under the applied experimental conditions, there were no significant changes of uterine weight as an indicator of estrogenic side effects.
D000475:Alkenes / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D004965:Estrogen Antagonists / Q000138:chemical synthesis; D005260:Female; D006801:Humans; D007536:Isomerism; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000627:therapeutic use; D013730:Terphenyl Compounds / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use*; D014599:Uterus / Q000033:anatomy & histology
D000475:Alkenes; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013730:Terphenyl Compounds; D013629:Tamoxifen