A series of coumarin-pargyline hybrids (4a-x) have been designed, synthesized and evaluated as novel dual inhibitors of Alzheimer's disease (AD). Most of the compounds exhibited a potent ability to inhibit amyloid-β (Aβ) aggregation and monoamine oxidases. In particular, compound 4x exhibited remarkable inhibitory activities against monoamine oxidases (IC₅₀, 0.027 ± 0.004 μM for MAO-B; 3.275 ± 0.040 μM for MAO-A) and Aβ_1-42 aggregation (54.0 ± 1.1%, 25 μM). Moreover, compound 4x showed low toxicity according to in vitro cell toxicity test. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that compound 4x would be potent to cross the blood-brain barrier. Collectively, these findings demonstrate that compound 4x was an effective and promising candidate for AD therapy.

已经设计，合成和评估了一系列香豆素-精氨酸-杂种化合物杂种（4a-x），作为阿尔茨海默氏病（AD）的新型双重抑制剂。大多数化合物显示有效的能力，以抑制淀粉样蛋白β（A β）聚集和单胺氧化酶。特别是，化合物4倍表现出对单胺氧化酶显着的抑制活性（IC ₅₀，0.027±0.004  μ M代表MAO-B; 3.275±0.040  μ M代表MAO-A）和A β _1-42聚集（54.0±1.1％，25  μ M）。此外，化合物4x根据体外显示低毒细胞毒性试验。血脑屏障的平行人工膜通透性测定结果表明，化合物4x可能会穿过血脑屏障。总的来说，这些发现表明化合物4x是AD疗法的有效和有希望的候选者。