Bibenzyl- and stilbene-core compounds with non-polar linker atom substituents as selective ligands for estrogen receptor beta.
A series of structurally simple bibenzyl-diol and stilbene-diol core molecules, structural analogs of the well-known hexestrol and diethylstilbestrol non-steroidal estrogens, were prepared and evaluated as estrogen receptor (ER) subtype-selective ligands. Analysis of their ERalpha and ERbeta binding showed that certain substitution patterns engendered binding affinities that were >100-fold selective for ERbeta. When further investigated in cell-based gene transcription assays, some molecules showed similarly high relative transcriptional potency selectivity in favor of ERbeta. Interestingly, the most ERbeta-selective molecules were those bearing non-polar substituents on one of the internal carbon atoms. These compounds should be useful probes for determining the physiological roles of ERbeta, and they might lead to the development of more selective and thus safer pharmaceuticals.
Waibel
Michael
M
Department of Chemistry, University of Illinois, 600 South Matthews Avenue, Urbana, IL 61801, United States.
De Angelis
Meri
M
Stossi
Fabio
F
Kieser
Karen J
KJ
Carlson
Kathryn E
KE
Katzenellenbogen
Benita S
BS
Katzenellenbogen
John A
JA
D001632:Bibenzyls / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D001632:Bibenzyls; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D013267:Stilbenes