Bis(4-hydroxyphenyl)[2-(phenoxysulfonyl)phenyl]methane: isolation and structure elucidation of a novel estrogen from commercial preparations of phenol red (phenolsulfonphthalein)

J Med Chem. 1988 Oct;31(10):1978-83. doi: 10.1021/jm00118a020.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Female
  • Magnetic Resonance Spectroscopy
  • Phenolphthaleins / analysis*
  • Phenolsulfonphthalein / analysis*
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Structure-Activity Relationship
  • Trityl Compounds / isolation & purification*
  • Uterus / drug effects

Substances

  • Phenolphthaleins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Trityl Compounds
  • bis(4-hydroxyphenyl)(2-(phenoxysulfonyl)phenyl)methane
  • Phenolsulfonphthalein