Bioorganic & Medicinal Chemistry Letters 2013-03-15

Synthesis of tetrahydroxybiphenyls and tetrahydroxyterphenyls and their evaluation as amyloid-β aggregation inhibitors.

Craig B Stevens, James M Hanna, Robin K Lammi

文献索引：Bioorg. Med. Chem. Lett. 23(6) , 1703-6, (2013)

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摘要

3,3',4,4'-Tetrahydroxybiphenyl and three isomeric 3,3″,4,4″-tetrahydroxyterphenyls with varying geometries around the central phenyl ring have been synthesized and evaluated for their in vitro activity against aggregation of Alzheimer's amyloid-β peptide (Aβ). Results from Congo red spectral-shift assays reveal that all four compounds successfully inhibit association of Aβ monomers. For the tetrahydroxyterphenyls, efficacy varies with linker geometry: the ortho-arrangement affords the most successful inhibition and the para-geometry the least, perhaps due to differing abilities of these compounds to bind Aβ. Of the four small molecules studied, 3,3',4,4'-tetrahydroxybiphenyl is the most effective inhibitor, reducing Aβ aggregation by 50% when present in stoichiometric concentrations.Copyright © 2013 Elsevier Ltd. All rights reserved.