Constrained phytoestrogens and analogues as ERbeta selective ligands

Bioorg Med Chem Lett. 2003 Jul 21;13(14):2399-403. doi: 10.1016/s0960-894x(03)00394-9.

Abstract

A new series of ERbeta (ERbeta) selective ligands has been prepared. One of the compounds 6, structurally related to the phytoestrogen apigenin 4, displays a binding preference for ERbeta over ERalpha of over 40-fold. In addition to its binding selectivity, 6 was able to potently induce metallothionein (an ERbeta specific response in human SAOS-2 cells) while demonstrating low potency in an ERalpha dependant ERE-tk luciferase assay in MCF-7 cells. Such receptor and cell selectivity could make 6 a useful molecular probe for better understanding the role of ERbeta in mammalian physiology.

MeSH terms

  • Alkylation
  • Apigenin
  • Cell Line
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Flavonoids / chemistry
  • Flavonoids / pharmacology
  • Gene Expression Regulation / drug effects
  • Genistein / chemical synthesis
  • Genistein / pharmacology
  • Humans
  • Indicators and Reagents
  • Isoflavones / chemical synthesis*
  • Isoflavones / chemistry
  • Isoflavones / pharmacology
  • Ligands
  • Luciferases / genetics
  • Metallothionein / biosynthesis
  • Phytoestrogens
  • Plant Preparations / chemical synthesis*
  • Plant Preparations / chemistry
  • Plant Preparations / pharmacology
  • Receptors, Estrogen / biosynthesis
  • Receptors, Estrogen / drug effects*
  • Receptors, Estrogen / genetics
  • Selective Estrogen Receptor Modulators / chemical synthesis*
  • Selective Estrogen Receptor Modulators / chemistry
  • Selective Estrogen Receptor Modulators / pharmacology
  • Structure-Activity Relationship

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Flavonoids
  • Indicators and Reagents
  • Isoflavones
  • Ligands
  • Phytoestrogens
  • Plant Preparations
  • Receptors, Estrogen
  • Selective Estrogen Receptor Modulators
  • Apigenin
  • Metallothionein
  • Genistein
  • Luciferases