Bis(4-hydroxyphenyl)methane: Isolation and Structure Elucidation of a Novel Estrogen from Commercial Preparations of Phenol Red (Phenolsulfonphthalein)

Article abstract of DOI:10.1021/jm00118a020

Commercial preparations of phenolsulfonphthalein (Phenol Red), a pH indicator dye widely added to cell culture media, have weak estrogenic activity that can be accounted for by a minor lipophilic impurity (ca. 0.002percent).We have isolated this impurity, determined its structure to be bis(4-hydroxyphenyl)<2-(phenoxysulfonyl)phenyl>methane, and synthesized it from phenolsulfonphthalein.This compound binds to the estrogen receptor with an affinity 50percent that of estradiol; it stimulates the proliferation and increases the progesterone receptor content of estrogen-responsive breast cancer cells in vitro, and stimulates uterine weight gain in rats in vivo, but shows a potency in these assays only 0.1-0.2percent that of estradiol.We suggest haw this novel estrogen may be generated during the preparation of phenolsulfonphthalein.