Polyfluorinated bis-styrylbenzenes as amyloid-β plaque binding ligands

Bioorg Med Chem. 2014 Apr 15;22(8):2469-81. doi: 10.1016/j.bmc.2014.02.054. Epub 2014 Mar 7.

Abstract

Detection of cerebral β-amyloid (Aβ) by targeted contrast agents remains of great interest to aid the in vivo diagnosis of Alzheimer's disease (AD). Bis-styrylbenzenes have been previously reported as potential Aβ imaging agents. To further explore their potency as (19)F MRI contrast agents we synthetized several novel fluorinated bis-styrylbenzenes and studied their fluorescent properties and amyloid-β binding characteristics. The compounds showed a high affinity for Aβ plaques on murine and human brain sections. Interestingly, competitive binding experiments demonstrated that they bound to a different binding site than chrysamine G. Despite their high logP values, many bis-styrylbenzenes were able to enter the brain and label murine amyloid in vivo. Unfortunately initial post-mortem (19)F NMR studies showed that these compounds as yet do not warrant further MRI studies due to the reduction of the (19)F signal in the environment of the brain.

Keywords: Alzheimer’s disease; Amyloid β; Contrast agent; Fluorine; Imaging.

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Benzene / chemistry*
  • Benzene / metabolism
  • Binding, Competitive
  • Brain / metabolism
  • Contrast Media / chemistry*
  • Contrast Media / metabolism
  • Drug Design
  • Fluorescent Dyes / chemistry
  • Fluorine / chemistry*
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Transgenic
  • Protein Binding
  • Spectrometry, Fluorescence

Substances

  • Amyloid beta-Peptides
  • Contrast Media
  • Fluorescent Dyes
  • Ligands
  • Fluorine
  • Benzene