Source:http://linkedlifedata.com/resource/pubmed/id/17035032
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2006-11-20
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pubmed:abstractText |
Several promising agents have been synthesized and evaluated for in vivo imaging probes of beta-amyloid plaques in Alzheimer's disease (AD) brain. Recently, we have developed flavone derivatives, which possess the basic structure of the 2-phenylchromone, as useful candidates for amyloid imaging agents. In an attempt to further develop novel tracers, we synthesized and evaluated a series of 2-styrylchromone derivatives, which replace the 2-phenyl substituent of flavone backbone with the 2-styryl. A series of radioiodinated styrylchromone derivatives were designed and synthesized. The binding affinities for amyloid plaques were assessed by in vitro binding assay using pre-formed synthetic Abeta(1-40) aggregates. The new series of styrylchromone derivatives showed high binding affinity to Abeta aggregates at the K(d) values of 32.0, 17.5 and 8.7nM for [(125)I]6, [(125)I]9, and [(125)I]12, respectively. In biodistribution studies using normal mice, [(125)I]6 and [(125)I]9 examined in normal mice displayed high brain uptakes with 4.9 and 2.8%ID/g at 2min post injection. The radioactivity washed out from the brain rapidly (1.6 and 1.0%ID/g at 60min post injection for [(125)I]6 and [(125)I]9, respectively). But [(125)I]12 did not show marked brain uptake, and the washout rate from the brain was relatively slow throughout the time course (1.1 and 1.4%ID/g at 2 and 30min post injection, respectively). Although additional modifications are necessary to improve the brain uptake and rapid clearance of non-specifically bound radiotracer, the styrylchromone backbone may be useful as a backbone structure to develop novel beta-amyloid imaging agents.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0968-0896
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
444-50
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17035032-Amyloid beta-Peptides,
pubmed-meshheading:17035032-Animals,
pubmed-meshheading:17035032-Binding, Competitive,
pubmed-meshheading:17035032-Binding Sites,
pubmed-meshheading:17035032-Chromones,
pubmed-meshheading:17035032-Drug Design,
pubmed-meshheading:17035032-Mice,
pubmed-meshheading:17035032-Molecular Structure,
pubmed-meshheading:17035032-Stereoisomerism,
pubmed-meshheading:17035032-Structure-Activity Relationship,
pubmed-meshheading:17035032-Tissue Distribution
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pubmed:year |
2007
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pubmed:articleTitle |
Synthesis and characterization of styrylchromone derivatives as beta-amyloid imaging agents.
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pubmed:affiliation |
Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. mono@nagasaki-u.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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