Pyrroloquinoxaline hydrazones as fluorescent probes for amyloid fibrils

Org Biomol Chem. 2011 Jul 21;9(14):5137-48. doi: 10.1039/c1ob05288h. Epub 2011 Jun 1.

Abstract

Here we describe the identification and preliminary characterization of a new class of pyrrolo(imidazo)quinoxaline hydrazones as florescent probes for Aβ(1-42) fibrils. All the newly developed compounds were able to bind amyloid fibrils formed in vitro and some of them displayed an increase of their fluorescence upon binding. When tested on brain tissue preparations presenting Aβ deposits, the described hydrazones selectively stained amyloid structures and did not display aspecific binding. The hydrazones did not show antifibrillogenic activity and electron microscopy analysis revealed that they do not interfere with fibrils structure. The described pyrrolo(imidazo)quinoxalines could be useful for studying amyloid structures in vitro. Moreover, their experimentally proven ability to cross the blood-brain barrier in mouse opens the possibility of developing these compounds as potential amyloid imaging agents for in vivo applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / chemical synthesis
  • Amyloid beta-Peptides / chemistry*
  • Animals
  • Brain / metabolism
  • Crystallography, X-Ray
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / pharmacokinetics
  • Hydrazones / blood
  • Hydrazones / chemistry*
  • Hydrazones / pharmacokinetics
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Molecular
  • Molecular Structure
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry*
  • Quinoxalines / blood
  • Quinoxalines / chemistry*
  • Quinoxalines / pharmacokinetics
  • Spectrometry, Fluorescence
  • Stereoisomerism
  • Tissue Distribution

Substances

  • Amyloid beta-Peptides
  • Fluorescent Dyes
  • Hydrazones
  • Peptide Fragments
  • Quinoxalines
  • amyloid beta-protein (1-42)