89778-47-2Relevant 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.
Synthesis and Antiestrogenic Activity of Diaryl Thioether Derivatives
Poirier, Donald,Auger, Serge,Merand, Yves,Simard, Jacques,Labrie, Fernand
, p. 1115 - 1125 (2007/10/02)
The reaction of 1,2-diarylethanol and mercapto side chain catalyzed by ZnI2 was used as a key step in the short (three to five steps) and efficient synthesis of 17 diaryl thioether derivatives.Several of these compounds contain a methyl butyl amide chain and an hydroxyaryl moiety, respectively, for antiestrogenic activity and binding affinity on estrogen receptor.No binding affinity for crude cytosolic preparation of the estrogen receptor was observed for compounds without phenolic group, while a low affinity (0.01-0.05percent) was measured for mono- or diphenol derivatives.Like the pure steroidal antiestrogen EM-139, these novel nonsteroidal compounds did not exert any stimulatory effect on cell proliferation of (ER+) ZR-75-1 human breast cancer cells and partially reversed the amplitude of the stimulatory effect induced by estradiol on this (ER+) cell line.No proliferative or antiproliferative effect on (ER-) MDA-MB-231 human breast cancer cells was also observed for three of these compounds (39-41).Among the newly synthesized nonsteroidal compounds, the thioether derivative 41 (N-butyl-N-methyl-13,14-bis(4'-hydroxyphenyl)-12-thiatetradecanamide), with a long methylbutylalkanamide side chain and a diphenolic nucleus, was selected as the best antiestrogenic compound.However, this compound was 100-fold less antiestrogenic in (ER+) ZR-75-1 cells than the steroidal antiestrogen EM-139.
