Synthesis and biological evaluation of p-carborane bisphenols and their derivatives: structure-activity relationship for estrogenic activity.
p-Carborane bisphenols and their derivatives were prepared and evaluated for binding affinity to estrogen receptor alpha. Their estrogenic activity was evaluated by means of transcriptional assay and cell proliferation assay using MCF-7 cell lines. 1,12-Bis(4-hydroxyphenyl)-1,12-dicarba-closo-dodecaborane 4a showed potent estrogenic activity, approaching that of 17beta-estradiol, in transactivation assay. The activity of isomers 5a and 6a was drastically affected by the change in the position of one of the hydroxyl groups; 6a (ortho-OH in one ring) was about 1000 times less potent than 4a. Modification of this hydroxyl group with alkyl groups decreased the estrogenic activity in all isomers. Compound 4a also showed potent MCF-7 cell proliferation-enhancing activity.
Ogawa
Takumi
T
Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Ohta
Kiminori
K
Iijima
Toru
T
Suzuki
Tomoharu
T
Ohta
Shigeru
S
Endo
Yasuyuki
Y
D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004958:Estradiol / Q000737:chemistry / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000378:metabolism; D004967:Estrogens / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
D001896:Boron Compounds; D047628:Estrogen Receptor alpha; D004967:Estrogens; D004958:Estradiol