Synthesis and characterization of novel phenylindoles as potential probes for imaging of β-amyloid plaques in the brain
| Autor: | Hideo Saji, Mamoru Haratake, Nobuya Kobashi, Hiroyuki Watanabe, Morio Nakayama, Masahiro Ono |
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| Rok vydání: | 2010 |
| Předmět: |
Biodistribution
Indoles Stereochemistry Ratón Clinical Biochemistry Pharmaceutical Science Plaque Amyloid Biochemistry Chemical synthesis Imaging Mice In vivo mental disorders Drug Discovery Pi medicine Animals Distribution (pharmacology) Tissue Distribution Molecular Biology Phenylindole Tomography Emission-Computed Single-Photon Indole test Amyloid beta-Peptides β-amyloid Chemistry Organic Chemistry Brain Alzheimer's disease medicine.disease Peptide Fragments Biophysics Molecular Medicine Radiopharmaceuticals |
| Zdroj: | Bioorganic & Medicinal Chemistry. 18:4740-4746 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2010.05.013 |
| Popis: | We synthesized a novel series of phenylindole (PI) derivatives and evaluated their biological activities as probes for imaging Abeta plaques in vivo. The affinity for Abeta plaques was assessed by an in vitro-binding assay using pre-formed synthetic Abeta aggregates. 2-Phenyl-1H-indole (2-PI) derivatives showed high affinity for Abeta42 aggregates with K(i) values ranging from 4 to 32nM. 2-PI derivatives clearly stained Abeta plaques in an animal model of AD. In biodistribution experiments using normal mice, 2-PI derivatives displayed sufficient uptake for imaging, ranging from 1.1% to 2.6% ID/g. Although additional modifications are necessary to improve uptake by and clearance from the brain, 2-PI derivatives may be useful as a backbone structure to develop novel Abeta imaging agents. Bioorganic & medicinal chemistry, 18(13), pp.4740-4746; 2010 |
| Databáze: | OpenAIRE |
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