jm5b01677_si_002.csv (2.67 kB)
Synthesis of Triphenylethylene Bisphenols as Aromatase Inhibitors That Also Modulate Estrogen Receptors
dataset
posted on 2016-01-14, 00:00 authored by Wei Lv, Jinzhong Liu, Todd C. Skaar, Elizaveta O’Neill, Ge Yu, David A. Flockhart, Mark CushmanA series
of triphenylethylene bisphenol analogues of the selective
estrogen receptor modulator (SERM) tamoxifen were synthesized and
evaluated for their abilities to inhibit aromatase, bind to estrogen
receptor α (ER-α) and estrogen receptor β (ER-β),
and antagonize the activity of β-estradiol in MCF-7 human breast
cancer cells. The long-range goal has been to create dual aromatase
inhibitor (AI)/selective estrogen receptor modulators (SERMs). The
hypothesis is that in normal tissue the estrogenic SERM activity of
a dual AI/SERM could attenuate the undesired effects stemming from
global estrogen depletion caused by the AI activity of a dual AI/SERM,
while in breast cancer tissue the antiestrogenic SERM activity of
a dual AI/SERM could act synergistically with AI activity to enhance
the antiproliferative effect. The potent aromatase inhibitory activities
and high ER-α and ER-β binding affinities of several of
the resulting analogues, together with the facts that they antagonize
β-estradiol in a functional assay in MCF-7 human breast cancer
cells and they have no E/Z isomers,
support their further development in order to obtain dual AI/SERM
agents for breast cancer treatment.