A series of (3-hydroxypyridin-4-one)-coumarin hybrids were developed and investigated as potential multitargeting candidates for the treatment of Alzheimer's disease (AD) through the incorporation of iron-chelating and monoamine oxidase B (MAO-B) inhibition. This combination endowed the hybrids with good capacity to inhibit MAO-B as well as excellent iron-chelating effects. The pFe³⁺ values of the compounds were ranging from 16.91 to 20.16, comparable to more potent than the reference drug deferiprone (DFP). Among them, compound 18d exhibited the most promising activity against MAO-B, with an IC₅₀ value of 87.9 nM. Moreover, compound 18d exerted favorable antioxidant activity, significantly reversed the amyloid-β_1-42 (Aβ_1-42) induced PC12 cell damage. More importantly, 18d remarkably ameliorated the cognitive dysfunction in a scopolamine-induced mice AD model. In brief, a series of hybrids with potential anti-AD effect were successfully obtained, indicating that the design of iron chelators with MAO-B inhibitory and antioxidant activities is an attractive strategy against AD progression.

通过结合铁螯合和单胺氧化酶B（MAO-B）抑制作用，开发并研究了一系列（3-羟基吡啶-4-酮）-香豆素杂合体，作为治疗阿尔茨海默氏病（AD）的潜在多靶点候选物。这种结合使杂种具有良好的抑制MAO-B的能力以及出色的铁螯合效果。化合物的pFe ^{3 +}值在16.91至20.16之间，比参考药物去铁酮（DFP）更有效。其中，化合物18d对MAO-B表现出最有希望的活性，IC ₅₀值为87.9 nM。此外，化合物18d具有良好的抗氧化活性，可显着逆转淀粉样蛋白β _1-42（A β _1-42）诱导的PC12细胞损伤。更重要的是，在东pol碱诱导的小鼠AD模型中18d明显改善了认知功能障碍。简而言之，成功获得了一系列具有潜在抗AD作用的杂种，表明具有MAO-B抑制和抗氧化活性的铁螯合剂的设计是对抗AD进展的有吸引力的策略。