Bis(4-hydroxyphenyl)[2-(phenoxysulfonyl)phenyl]methane: isolation and structure elucidation of a novel estrogen from commercial preparations of phenol red (phenolsulfonphthalein)
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. 0.002%). 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 50% that of estradiol; it stimulates the proliferation and increases the progesterone receptor content of estrogen-responsive breast cancer cells in vitro, and it stimulates uterine weight gain in rats in vivo, but shows a potency in these assays only 0.1-0.2% that of estradiol. We suggest how this novel estrogen may be generated during the preparation of phenolsulfonphthalein.
Bindal
R D
RD
Department of Chemistry, University of Illinois, Urbana 61801.
Katzenellenbogen
J A
JA
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D010635:Phenolphthaleins / Q000032:analysis*; D010637:Phenolsulfonphthalein / Q000032:analysis*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013329:Structure-Activity Relationship; D014320:Triphenylmethyl Compounds / Q000302:isolation & purification*; D014599:Uterus / Q000187:drug effects
D010635:Phenolphthaleins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014320:Triphenylmethyl Compounds; C057369:bis(4-hydroxyphenyl)(2-(phenoxysulfonyl)phenyl)methane; D010637:Phenolsulfonphthalein