4120-45-0Relevant academic research and scientific papers
Structure-function relationships of estrogenic triphenylethylenes related to endoxifen and 4-hydroxytamoxifen
Maximov, Philipp Y.,Myers, Cynthia B.,Curpan, Ramona F.,Lewis-Wambi, Joan S.,Jordan, V. Craig
experimental part, p. 3273 - 3283 (2010/09/09)
Estrogens can potentially be classified into planar (class I) or nonplanar (class II) categories, which might have biological consequences. 1,1,2-Triphenylethylene (TPE) derivatives were synthesized and evaluated against 17β-estradiol (E2) for their estrogenic activity in MCF-7 human breast cancer cells. All TPEs were estrogenic and, unlike 4-hydroxytamoxifen (4OHTAM) and Endoxifen, induced cell growth to a level comparable to that of E2. All the TPEs increased ERE activity in MCF-7:WS8 cells with the order of potency as followed: E2 > 1,1-bis(4,4′-hydroxyphenyl)-2-phenylbut-1-ene (15) > 1,1,2-tris(4-hydroxyphenyl)but-1-ene (3) > Z 4-(1-(4-hydroxyphenyl)-1- phenylbut-1-en-2-yl)phenol (7) > E 4-(1-(4-hydroxyphenyl)-1-phenylbut-1-en-2- yl)phenol (6) > Z(4-(1-(4-ethoxyphenyl)-1-(4-hydroxyphenyl)but-1-en-2-yl) phenol (12) > 4-OHTAM. Transient transfection of the ER-negative breast cancer cell line T47D:C4:2 with wild-type ER or D351G ER mutant revealed that all of the TPEs increased ERE activity in the cells expressing the wild-type ER but not the mutant, thus confirming the importance of Asp351 for ER activation by the TPEs. The findings confirm E2 as a class I estrogen and the TPEs as class II estrogens. Using available conformations of the ER liganded with 4OHTAM or diethylstilbestrol, the TPEs optimally occupy the 4OHTAM ER conformation that expresses Asp351.
1,1,2-Triphenylbut-1-enes: Relationship between Structure, Estradiol Receptor Affinity, and Mammary Tumor Inhibiting Properties
Schneider, Martin R.,Angerer, Erwin von,Schoenenberger, Helmut,Michel, Ralf Th.,Fortmeyer, H. P.
, p. 1070 - 1077 (2007/10/02)
1,1,2-Triphenylbut-1-enes, which are substituted with acetoxy groups on one, two, or three aromatic rings in the para and/or meta positions, were synthesized.The identity of the occurring E and Z isomers were established by 1H NMR spectroscopy.A study on structure-activity relationships was carried out with regard to estradiol receptor affinity and to inhibiting effects on the growth of a postmenopausal human mammary carcinoma implanted in nude mice.The para-substituted compounds generally exhibited a higher receptor affinity and a better antitumor activity than the corresponding meta-substituted ones.The E isomers were superior to the respective Z isomers in those two properties.The tumor-inhibiting effect of the mono-and disubstituted compounds was better than that of the trisubstituted ones.Except for the trisubstituted compounds, they all showed a good correlation between estradiol receptor affinity and antitumor activity.One of the compounds was also tested on the 9,10-dimethylbenzanthracene-induced, hormone-dependent mammary carcinoma of the Spraque-Dawley rat, and the results corresponded to those obtained in the xenograft tumor.
