BODIPY-17α-ethynylestradiol conjugates: Synthesis, fluorescence properties and receptor binding affinities

Bioorg Med Chem Lett. 2017 Feb 1;27(3):443-446. doi: 10.1016/j.bmcl.2016.12.052. Epub 2016 Dec 25.

Abstract

In vivo imaging of estrogen receptor (ER) densities in human breast cancer is a potential tool to stage disease, guide treatment protocols and follow-up on treatment outcome. Both positron emission tomography (PET) and fluorescence imaging have received ample attention to detect ligand-ER interaction. In this study we prepared BODIPY-estradiol conjugates using 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) as fluorescent probe and estradiol derivatives as ligand and established their relative binding affinity (RBA) for the ERα. The synthesis of the conjugates involves attachment of a BODIPY moiety to the C17α-position of estradiol using Sonogashira or click reactions of iodo-BODIPY or aza-BODIPY with various 17α-ethynylestradiol (EE2) derivatives. The highest RBA for the ERα was observed with the EE2-BODIPY conjugate (7) featuring a linear eight carbon spacer chain. Cell uptake studies and in vivo imaging experiments in an ER-positive mouse tumor model are in progress.

Keywords: 17α-Ethynylestradiol conjugates; BODIPY; Estrogen receptor; Fluorescence imaging; RBA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boron Compounds / chemistry*
  • Breast Neoplasms / diagnostic imaging
  • Click Chemistry
  • Contrast Media / chemical synthesis*
  • Contrast Media / chemistry
  • Contrast Media / metabolism
  • Estrogen Receptor alpha / chemistry
  • Estrogen Receptor alpha / metabolism*
  • Ethinyl Estradiol / chemistry*
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Positron-Emission Tomography
  • Protein Binding
  • Spectrometry, Fluorescence

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Boron Compounds
  • Contrast Media
  • Estrogen Receptor alpha
  • Ethinyl Estradiol