Polyfluorinated bis-styrylbenzene β-amyloid plaque binding ligands

Daniel P. Flaherty, Shannon M. Walsh, Tomomi Kiyota, Yuxiang Dong, Tsuneya Ikezu, Jonathan L. Vennerstrom

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

β-Amyloid (Aβ) binding affinities and specificities for six bis-styrylbenzenes with multiple magnetically equivalent fluorine atoms in the form of a tetrafluorophenyl core or symmetrical trifluoromethyl and trifluoromethoxy groups were determined by means of fluorescence titrations with amyloid peptide Aβ1-40 and a novel in vitro fluorescence-based assay using APP/PS1 transgenic mouse brain sections. Bisstyrylbenzenes with a tetrafluorophenyl core had increased Aβ binding affinities compared to their monofluorophenyl or phenyl counterparts. Bis-styrylbenzenes with carboxylic acid functional groups had lower Aβ binding affinities than their neutral counterparts. Selected bis-styrylbenzenes were demonstrated to have good blood - brain barrier penetration capabilities. These data extend the SAR of bis-styrylbenzene Aβ binding and provide direction for the development of a noninvasive probe for early detection of Alzheimer's disease using 19F MRI.

Original languageEnglish (US)
Pages (from-to)4986-4992
Number of pages7
JournalJournal of Medicinal Chemistry
Volume50
Issue number20
DOIs
StatePublished - Oct 20 2007

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Amyloid Plaques
Amyloid
Fluorescence
Ligands
Fluorine
Carboxylic Acids
Blood-Brain Barrier
Titration
Magnetic resonance imaging
Functional groups
Transgenic Mice
Early Diagnosis
Assays
Brain
Alzheimer Disease
Atoms
Peptides
Direction compound
In Vitro Techniques
Fluorine-19 Magnetic Resonance Imaging

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Polyfluorinated bis-styrylbenzene β-amyloid plaque binding ligands. / Flaherty, Daniel P.; Walsh, Shannon M.; Kiyota, Tomomi; Dong, Yuxiang; Ikezu, Tsuneya; Vennerstrom, Jonathan L.

In: Journal of Medicinal Chemistry, Vol. 50, No. 20, 20.10.2007, p. 4986-4992.

Research output: Contribution to journalArticle

Flaherty, Daniel P. ; Walsh, Shannon M. ; Kiyota, Tomomi ; Dong, Yuxiang ; Ikezu, Tsuneya ; Vennerstrom, Jonathan L. / Polyfluorinated bis-styrylbenzene β-amyloid plaque binding ligands. In: Journal of Medicinal Chemistry. 2007 ; Vol. 50, No. 20. pp. 4986-4992.
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