A series of salicylamide derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors. They showed good inhibitory activities of self- and Cu2+-induced Aβ1-42 aggregation, and significant antioxidant activities. Among them, compound 15b exhibited good inhibitory activity toward RatAChE and EeAChE with IC50 value of 10.4 μM and 15.2 μM, respectively. Moreover, 15b displayed high antioxidant activity (2.46 Trolox equivalents), good self- and Cu2+-induced Aβ1-42 aggregation inhibitory potency (42.5% and 31.4% at 25.0 μM, respectively) and moderate disaggregation ability to self- and Cu2+-induced Aβ1-42 aggregation fibrils (23.4% and 27.0% at 25 μM, respectively). Furthermore, 15b also showed biometal chelating abilities, anti-neuroinflammatory ability and BBB permeability. These multifunctional properties indicated compound 15b was worthy of being chosen for further pharmacokinetics, toxicity and behavioral researches to test its potential for AD treatment.

中文翻译：

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新型水杨酰胺衍生物作为有效的多功能药物，可治疗阿尔茨海默氏病：设计，合成和生物学评估。

设计，合成和评估了一系列水杨酰胺衍生物，作为治疗阿尔茨海默氏病的多功能药物。体外测定表明，大多数衍生物是选择性的AChE抑制剂。他们表现出良好的自我和Cu2 +诱导的Aβ1-42聚集的抑制活性，以及​​显着的抗氧化活性。其中，化合物15b显示出对RatAChE和EeAChE的良好抑制活性，IC 50值分别为10.4μM和15.2μM。此外，15b表现出较高的抗氧化活性（2.46 Trolox当量），良好的自我和Cu2 +诱导的Aβ1-42聚集抑制能力（在25.0μM时分别为42.5％和31.4％）以及对自我和Cu2 +诱导的Aβ1的中等分解能力。 -42聚集原纤维（25μM时分别为23.4％和27.0％）。此外，图15b还显示了生物金属螯合能力，抗神经炎能力和BBB通透性。这些多功能特性表明，化合物15b值得选择用于进一步的药代动力学，毒性和行为研究，以测试其在AD治疗中的潜力。