Synthesis and evaluation of 17alpha-arylestradiols as ligands for estrogen receptor alpha and beta.
To identify novel estrogen receptor ligands a series of substituted 17alpha-arylestradiols were synthesized using the catalytic [2 + 2 + 2]cyclotrimerization of 17alpha-ethynylestradiol with various 1,7-diynes in the presence of Wilkinson's catalysts [Rh(PPh(3))(3)Cl]. The compounds were subjected to competitive binding assays, cell-based luciferase reporter assays, and proliferation assays. These experiments confirmed their estrogenic character and revealed some interesting properties like mixed partial/full agonism for ERalpha/ERbeta and different selectivity as a result of differing potencies for either ER.
Sedlák
David
D
Center for Chemical Genetics, Institute of Molecular Genetics, vvi, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Novák
Petr
P
Kotora
Martin
M
Bartůnek
Petr
P
D000480:Alkynes / Q000737:chemistry; D001667:Binding, Competitive; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003500:Cyclization; D054333:Drug Partial Agonism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000235:genetics; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000235:genetics; D005454:Fluorescence Polarization; D017930:Genes, Reporter; D006801:Humans; D008024:Ligands; D008156:Luciferases / Q000235:genetics; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
D000480:Alkynes; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D004958:Estradiol; D008156:Luciferases