Phenolic Bis-styrylbenzenes as beta-Amyloid Binding Ligands and Free Radical Scavengers

作者：Flaherty Daniel P; Kiyota Tomomi; Dong Yuxiang; Ikezu Tsuneya; Vennerstrom Jonathan L^*

来源：Journal of Medicinal Chemistry, 2010, 53(22): 7992-7999.

DOI：10.1021/jm1006929

Starting from bisphenolic bis-styrylbenzene DF-9 (4), P-amyloid (A beta) binding affinity and specificity for phenolic bis-styrylbenzenes, monostyrylbenzenes, and alkyne controls were determined by fluorescence titration with beta-amyloid peptide A beta(1-40) and a fluorescence assay using APP/PSI transgenic mouse brain sections. Bis-styrylbenzene SA R is derived largely from work on symmetrical compounds. This study is the first to describe A beta 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 A beta binding affinity and specificity comparable to 4 was its 3-hydroxy regioisomer 8. Like 4, 8 crossed the blood brain barrier and bound to A beta plaques in vivo. By use of a DPPH assay, phenol functional groups with papa orientations seem to be a necessary. but insufficient, criterion for good free radical scavenging properties in these compounds.

• 出版日期2010-11-25