Effect of fluorination on the pharmacological profile of 11beta isomers of fulvestrant in breast carcinoma cells

J Med Chem. 2009 Feb 12;52(3):883-7. doi: 10.1021/jm801154q.

Abstract

We describe the synthesis of an 11beta isomer 3 of the steroidal antiestrogen fulvestrant 2. Partial fluorination of the 11beta side chain in 3 leads to 4, which still shows strong antiproliferative activity on MCF-7 cells. However, unlike 2 and 3, compound 4 fails to down-regulate estrogen receptor alpha (ERalpha). This result suggests that ERalpha down-regulation is not a sine qua non condition for the antitumor activity of steroidal antiestrogens.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms
  • Cell Line, Tumor
  • Down-Regulation
  • Estradiol / analogs & derivatives*
  • Estradiol / chemical synthesis
  • Estradiol / chemistry
  • Estradiol / pharmacology
  • Estrogen Receptor Modulators / chemical synthesis
  • Estrogen Receptor Modulators / pharmacology*
  • Estrogen Receptor alpha / drug effects
  • Fulvestrant
  • Humans

Substances

  • Antineoplastic Agents
  • Estrogen Receptor Modulators
  • Estrogen Receptor alpha
  • Fulvestrant
  • Estradiol