Phenolic bis-styrylbenzenes as β-amyloid binding ligands and free radical scavengers

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

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Starting from bisphenolic bis-styrylbenzene DF-9 (4), β-amyloid (Aβ) binding affinity and specificity for phenolic bis-styrylbenzenes, monostyrylbenzenes, and alkyne controls were determined by fluorescence titration with β-amyloid peptide Aβ1-40 and a fluorescence assay using APP/PS1 transgenic mouse brain sections. Bis-styrylbenzene SAR is derived largely from work on symmetrical compounds. This study is the first to describe Aβ binding data for bis-styrylbenzenes unsymmetrical in the outer rings. With one exception, binding affinity and specificity were decreased by adding and/or changing the substitution pattern of phenol functional groups, changing the orientation about the central phenyl ring, replacing the alkene with alkyne bonds, or eliminating the central phenyl ring. The only compound with an Aβ binding affinity and specificity comparable to 4 was its 3-hydroxy regioisomer 8. Like 4, 8 crossed the blood-brain barrier and bound to Aβ plaques in vivo. By use of a DPPH assay, phenol functional groups with para orientations seem to be a necessary, but insufficient, criterion for good free radical scavenging properties in these compounds.

Original languageEnglish (US)
Pages (from-to)7992-7999
Number of pages8
JournalJournal of Medicinal Chemistry
Volume53
Issue number22
DOIs
StatePublished - Nov 25 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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