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

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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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.

Original languageEnglish
Pages (from-to)7724-7730
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number22
DOIs
Publication statusPublished - 2010 Nov 15

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Hong, M. C., Kim, Y. K., Choi, J. Y., Yang, S. Q., Rhee, H., Ryu, Y. H., Choi, T. H., Cheon, G. J., An, G. I., Kim, H. Y., Kim, Y., Kim, D. J., Lee, J. S., Chang, Y. T., & Lee, K. C. (2010). Synthesis and evaluation of stilbene derivatives as a potential imaging agent of amyloid plaques. Bioorganic and Medicinal Chemistry, 18(22), 7724-7730. https://doi.org/10.1016/j.bmc.2010.06.044