Fifteen chalcone derivatives 3a–3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self-induced Aβ_1-42 aggregation effectively ranged from 45.9–94.5 % at 20 μM, and acted as potential antioxidants. Their structure-activity relationships were summarized. In particular, (2E)-3-[4-(dimethylamino)phenyl]-1-(pyridin-2-yl)prop-2-en-1-one (3g) exhibited an excellent inhibitory activity of 94.5 % at 20 μM, and it could disassemble the self-induced Aβ_1-42 aggregation fibrils with ratio of 57.1 % at 20 μM concentration. In addition, compound 3g displayed good chelating ability for Cu²⁺, and could effectively inhibit and disaggregate Cu²⁺-induced Aβ aggregation. Moreover, compound 3g exerted low cytotoxicity, significantly reversed Aβ_1-42-induced SH-SY5Y cell damage. More importantly, compound 3g remarkably ameliorated scopolamine-induced memory impairment in mice. In summary, all the results revealed compound 3g was a potential multifunctional agent for AD therapy.

中文翻译：

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查耳酮衍生物作为抗阿尔茨海默病的多功能药物的设计、合成和评估

合成了15 种查耳酮衍生物3a – 3o，并作为抗阿尔茨海默病的多功能药物进行了评估。体外研究表明，这些化合物在 20 μM 时有效抑制自诱导 Aβ _1-42聚集的范围为 45.9–94.5 %，并充当潜在的抗氧化剂。总结了它们的构效关系。特别是，( 2E )-3-[4-(二甲基氨基)苯基]-1-(吡啶-2-基)丙-2-烯-1-酮( 3g )在20℃时表现出94.5%的优异抑制活性μM，在20 μM浓度下可分解自诱导的Aβ _1-42聚集原纤维，比例为57.1 %。另外，复方3g对Cu ²⁺表现出良好的螯合能力，能有效抑制和解聚Cu ²⁺诱导的Aβ聚集。此外，化合物3g具有低细胞毒性，显着逆转 Aβ _1-42诱导的 SH-SY5Y 细胞损伤。更重要的是，化合物3g显着改善了东莨菪碱引起的小鼠记忆障碍。总之，所有结果表明化合物3g是一种潜在的 AD 治疗多功能药物。