title: Synthesis and evaluation of stilbene derivatives as a potential imaging agent of amyloid plaques.
abstract: 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.
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 215-4, Seoul 139-706, Republic of Korea.
authors.forename: Myeng Chan
authors.initials: MC
authors.lastname: Hong
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Kim
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Choi
authors.forename: Si Qiang
authors.initials: SQ
authors.lastname: Yang
authors.forename: Hakjune
authors.initials: H
authors.lastname: Rhee
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Ryu
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Choi
authors.forename: Gi Jeong
authors.initials: GJ
authors.lastname: Cheon
authors.forename: Gwang Il
authors.initials: GI
authors.lastname: An
authors.forename: Hye Yun
authors.initials: HY
authors.lastname: Kim
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Kim
authors.forename: Jun-Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Chang
authors.forename: Kyo Chul
authors.initials: KC
authors.lastname: Lee
mesh_terms: 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
chemical_list: C555997:4-N-methyl-4'-bromostilbene; C496816:4-N-methylamino-4'-hydroxystilbene; D005456:Fluorescent Dyes; D013267:Stilbenes