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 α. 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 17β-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.

Carborane as a spherical hydrophobic pharmacophore: A series of p-carborane bisphenol derivatives were designed and synthesized as candidate estrogen receptor α (ERα) ligands. Bis(4-hydroxyphenyl)-p-carborane showed high binding affinity for human ERα and potent estrogenic activity in transactivation and cell proliferation assays with MCF-7 cells.Figure optionsDownload as PowerPoint slide