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 Scopus citations

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
Publication statusPublished - Oct 20 2007

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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