Department of Chemistry, Physics, and Geology, Winthrop University, 101 Sims Science Building, Rock Hill, SC 29733, United States.
Bioorg Med Chem Lett. 2013 Mar 15;23(6):1703-6. doi: 10.1016/j.bmcl.2013.01.076. Epub 2013 Feb 4.
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.
3,3',4,4'-四羟基联苯和三种具有不同中心苯环几何构型的 3,3″,4,4″-四羟基三苯均已合成，并对其体外抑制阿尔茨海默病淀粉样β肽（Aβ）聚集的活性进行了评价。刚果红光谱位移测定结果表明，这四种化合物均能成功抑制 Aβ单体的聚集。对于四羟基三苯，其功效随连接体几何形状而变化：邻位排列提供最成功的抑制作用，而对位几何形状则提供最小的抑制作用，这可能是由于这些化合物结合 Aβ的能力不同所致。在所研究的四种小分子中，3,3',4,4'-四羟基联苯是最有效的抑制剂，当以化学计量浓度存在时，可使 Aβ聚集减少 50%。
