Stereochemistry of cis- and trans-hinokiresinol and their estrogen-like activity.
Naturally occurring phenylpropanoids, hinokiresinol (trans-hinokiresinol) and nyasol (cis-hinokiresinol) were found to possess appreciable estrogen receptor binding activity. Strong differences in activity were observed between the geometrical isomers and enantiomers. Among these, (3S)-cis-hinokiresinol displayed the highest activity, one order of magnitude greater than the activity of genistein. Furthermore, cis- and trans-hinokiresinol stimulated the proliferation of estrogen-dependent T47D breast cancer cells, and their stimulatory effects were blocked by an estrogen antagonist, indicating that the compounds are estrogen agonists. In addition, the absolute configuration of C-3 in (+)-cis-hinokiresinol has been assigned as S by comparison with the circular dichroism spectra of the hydrogenated products prepared from cis and trans ((3S)-trans-hinokiresinol: previously assigned) isomers. These results incidentally provide us with an unambiguous answer to contradictory reports regarding the assignment of the full stereochemisry of cis- and trans-hinokiresinol that have existed in the literature for more than two decades.
Minami
E
E
Exploratory Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Taki
M
M
Takaishi
S
S
Iijima
Y
Y
Tsutsumi
S
S
Akiyama
T
T
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007529:Isoflavones; D017705:Lignans; D009682:Magnetic Resonance Spectroscopy; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology*; D048789:Phytoestrogens; D028321:Plant Preparations; D010946:Plants, Medicinal / Q000737:chemistry; D053284:Polyunsaturated Alkamides; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D017705:Lignans; D010636:Phenols; D048789:Phytoestrogens; D028321:Plant Preparations; D053284:Polyunsaturated Alkamides; C119821:hinokiresinol; D004958:Estradiol; C051781:ICI 164384