Synthesis, characterization, and estrogen receptor binding affinity of flavone-, indole-, and furan-estradiol conjugates

Bioorg Med Chem Lett. 2007 Jun 1;17(11):3212-6. doi: 10.1016/j.bmcl.2007.03.016. Epub 2007 Mar 12.

Abstract

Different flavone-, indole-, and furan-17beta-estradiol conjugates, linked via alkyl spacer chains extending from the 17alpha-position of the estradiol moiety, were synthesized by Pd-catalyzed cross-coupling reactions. Structures were assigned based on spectroscopic data. In vitro competitive binding assays for the estrogen receptor (alpha-ER), using [(3)H]estradiol (RBA=100) as a competitor, revealed that a two-carbon alkyl linker combined with a flavone conjugate provided the highest binding affinity (RBA approximately 9), warranting further studies on their potential use as selective estrogen-receptor modulators (SERMs) for hormone-replacement therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive
  • Catalysis
  • Estradiol / chemistry*
  • Estrogen Receptor alpha / chemistry*
  • Estrogen Receptor alpha / drug effects
  • Estrogens, Conjugated (USP) / chemical synthesis
  • Estrogens, Conjugated (USP) / chemistry*
  • Estrogens, Conjugated (USP) / pharmacology
  • Flavones / chemistry*
  • Furans / chemistry*
  • Indoles / chemistry*
  • Molecular Structure
  • Palladium / chemistry
  • Selective Estrogen Receptor Modulators / chemical synthesis
  • Selective Estrogen Receptor Modulators / chemistry
  • Selective Estrogen Receptor Modulators / pharmacology

Substances

  • Estrogen Receptor alpha
  • Estrogens, Conjugated (USP)
  • Flavones
  • Furans
  • Indoles
  • Selective Estrogen Receptor Modulators
  • Estradiol
  • Palladium