Synthesis and evaluation of stilbene derivatives as a potential imaging agent of amyloid plaques.
Fluorescence probes that can detect Aβ (β-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 Aβ40 fibrils in vitro. Four compounds exhibited more than sixfold intensity increase, and they were further analyzed for detail bindings and Aβ 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±0.37μM. In AD mouse brain tissue, 42 selectively stained Aβ plaque, more specifically peripheral regions of Aβ plaque. This finding demonstrated its potential use as brain-imaging agents for AD studies.
Hong
Myeng Chan
MC
Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 215-4, Seoul 139-706, Republic of Korea.
Kim
Yun Kyung
YK
Choi
Jae Yong
JY
Yang
Si Qiang
SQ
Rhee
Hakjune
H
Ryu
Young Hoon
YH
Choi
Tae Hyun
TH
Cheon
Gi Jeong
GJ
An
Gwang Il
GI
Kim
Hye Yun
HY
Kim
Youngsoo
Y
Kim
Dong Jin
DJ
Lee
Jun-Seok
JS
Chang
Young-Tae
YT
Lee
Kyo Chul
KC
D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D051379:Mice; D058225:Plaque, Amyloid / Q000737:chemistry* / Q000378:metabolism; D049268:Positron-Emission Tomography; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry*; D015899:Tomography, Emission-Computed, Single-Photon
C555997:4-N-methyl-4'-bromostilbene; C496816:4-N-methylamino-4'-hydroxystilbene; D005456:Fluorescent Dyes; D013267:Stilbenes