Acetoxy-substituted 1,1,2-triphenylbut-1-enes with antiestrogenic and mammary tumor inhibiting properties

Abstract

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)-1-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.