Synthesis and evaluation of stilbene derivatives as a potential imaging agent of amyloid plaques

Abstract

Fluorescence probes that can detect A beta (beta-amyloid peptide) plaque are important tools for diagnosis of Alzheimer's disease (AD), and 4-N-methylamino-4'-hydroxystilbene (SB-13) is one of the promising candidate molecules. We report here the synthesis of SB-13 derivatives that consist of various electron donating/withdrawing moieties and distinct size of N-substituents. The synthesized compounds were screened for detection of A beta 40 fibrils in vitro. Four compounds exhibited more than sixfold intensity increase, and they were further analyzed for detail bindings and A beta plaque imaging. Among these molecules, compound 42 meets two critical requirements for imaging agent; high fluorescence responsiveness and strong binding affinity. This compound showed more than 25-fold increase with the dissociation constant of 1.13 +/- 0.37 mu M. In AD mouse brain tissue, 42 selectively stained A beta plaque, more specifically peripheral regions of A beta plaque. This finding demonstrated its potential use as brain-imaging agents for AD studies. (C) 2010 Elsevier Ltd. All rights reserved.