Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125-3393, USA.
Bioorg Med Chem Lett. 2013 May 1;23(9):2614-8. doi: 10.1016/j.bmcl.2013.02.103. Epub 2013 Mar 14.
A series of compounds containing an α,β-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimer's disease (AD) agents. The investigations included the inhibition of cholinesterases (AChE, BuChE), the inhibition of amyloid beta (Aβ) self-assembly and the disassembly of preformed Aβ oligomers. Several compounds showed excellent potential as multifunctional compounds for AD. Docking studies for 16 that performed well in all the assays gave a clear interpretation of various interactions in the gorge of AChE. Based on the results, the long-chain coumarin scaffold appears to be a promising structural template for further AD drug development.
设计、合成并测试了一系列含有α,β-不饱和羰基部分的化合物，如查耳酮和香豆素，以评估它们作为抗阿尔茨海默病（AD）药物的潜力。这些研究包括抑制乙酰胆碱酯酶（AChE、BuChE）、抑制淀粉样β（Aβ）自组装和分解已形成的 Aβ 寡聚物。一些化合物表现出作为多功能 AD 化合物的巨大潜力。对在所有测定中表现良好的 16 个化合物进行的对接研究清楚地解释了 AChE 峡谷中的各种相互作用。基于这些结果，长链香豆素支架似乎是进一步开发 AD 药物的有前途的结构模板。
