title: Synthesis of tetrahydroxybiphenyls and tetrahydroxyterphenyls and their evaluation as amyloid-β aggregation inhibitors.
abstract: 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.
authors: Department of Chemistry, Physics, and Geology, Winthrop University, 101 Sims Science Building, Rock Hill, SC 29733, United States.
authors: Craig B
authors: CB
authors: Stevens
authors: James M
authors: JM
authors: Hanna
authors: Robin K
authors: RK
authors: Lammi
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D003224:Congo Red / Q000737:chemistry; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D013730:Terphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D001713:Biphenyl Compounds; D003224:Congo Red; D010446:Peptide Fragments; D013730:Terphenyl Compounds; C078592:amyloid beta-protein (1-40); C010574:biphenyl
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