Synthesis and evaluation of stilbenylbenzoxazole and stilbenylbenzothiazole derivatives for detecting beta-amyloid fibrils.
This paper describes a novel series of stilbenylbenzoxazole (SBO) and stilbenylbenzothiazole (SBT) derivatives for beta-amyloid specific binding probes. These 24 compounds were synthesized and evaluated by competitive binding assay against beta-amyloid 1-42 (Abeta42) aggregates using [(125)I]TZDM. All the derivatives displayed higher binding affinities with K(i) value in the subnanomolar range (0.10-0.74 nM) than Pittsburgh Compound-B (PIB) (0.77 nM). Among these derivatives, SBT-2, 5-fluoroethoxy-2-{4-[2-(4-methylaminophenyl)vinyl]phenyl}benzothiazole, showed lowest K(i) value (0.10 nM). In conclusion, the preliminary results suggest that these compounds are implying a possibility as a probe for detection of Abeta fibrils in Alzheimer's disease (AD) patients.
Lee
Ji Hoon
JH
Center for Chemoinformatics Research, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Byeon
Seong Rim
SR
Lim
Soo Jeong
SJ
Oh
Seung Jun
SJ
Moon
Dae Hyuk
DH
Yoo
Kyung Ho
KH
Chung
Bong Young
BY
Kim
Dong Jin
DJ
D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000737:chemistry; D007457:Iodine Radioisotopes / Q000737:chemistry; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism*; D049268:Positron-Emission Tomography; D051381:Rats; D013267:Stilbenes / Q000138:chemical synthesis* / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D013267:Stilbenes; C075222:amyloid beta-protein (1-42)