Synthesis and evaluation of stilbene derivatives as a potential imaging agent of amyloid plaques |
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Authors: | Myeng Chan Hong Yun Kyung Kim Jae Yong Choi Si Qiang Yang Hakjune Rhee Young Hoon Ryu Tae Hyun Choi Gi Jeong Cheon Gwang Il An Hye Yun Kim Youngsoo Kim Dong Jin Kim Jun-Seok Lee Young-Tae Chang Kyo Chul Lee |
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Affiliation: | 1. Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 215-4, Seoul 139-706, Republic of Korea;2. Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543, Singapore;3. Department of Chemistry and Applied Chemistry, Hanyang University, 1271 Sa-3-Dong Sanrgok-Gu, Ansan, Kyunggi-Do 426-791, Republic of Korea;4. Department of Nuclear Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, 612 Eonjuro, Kangnam-Gu, Seoul 135-720, Republic of Korea;5. Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore 138667, Singapore;6. Life/Health Division, Integrated Omics Center, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea;7. Life/Health Division, Neuro-medicine Center, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea |
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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 ± 0.37 μM. 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. |
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