Lv, WeiLiu, JinzhongSkaar, Todd C.O'Neill, ElizavetaYu, GeFlockhart, David A.Cushman, Mark2016-08-172016-08-172016Lv, W., Liu, J., Skaar, T. C., O’Neill, E., Yu, G., Flockhart, D. A., & Cushman, M. (2016). Synthesis of Triphenylethylene Bisphenols as Aromatase Inhibitors That Also Modulate Estrogen Receptors. Journal of Medicinal Chemistry, 59(1), 157–170. http://doi.org/10.1021/acs.jmedchem.5b01677https://hdl.handle.net/1805/10710A 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.enPublisher Policyaromataseselective estrogen receptor modulatorsbreast cancer treatmentArticle