Alzheimer's disease is characterized by amyloid β aggregation and cholinergic neurodegeneration. In the present study, pure DDN (2,3‐dichloro‐5,8‐dihydroxy‐1,4‐naphthoquinone) was examined, for the first time, for its dual potential as inhibitor of acetylcholinesterase (AChE) and Aβ₄₂ aggregation. Such investigation was encouraged by the in vitro high antioxidant potential of DDN. Indeed, it revealed interesting antioxidant activity with IC₅₀ values of 9.8 and 4.3 µM for ABTS and reducing power, respectively. The ability of DDN to counteract Aβ₄₂ aggregation was evaluated by thioflavine‐T assay. Strong inhibition of Aβ₄₂ aggregation of more than 90% at 25 µM was measured. Moreover, results showed that DDN inhibited AChE (IC₅₀ = 14.5 µM). To better understand the interactions between DDN and AChE, molecular docking was performed. Obtained data predicted a high interaction characterized by hydrogen bonding at TYR337 as for galanthamine (positive control). Several residues involved in AChE hydrophobic interactions were similarly implicated in binding of this domain to DDN (ASP74, THR83, and TYR124). All these data would be useless if DDN could not pass the blood–brain barrier. So, DDN was loaded into alginate microspheres to enhance its stability and bioavailability. Thereafter, drug release profiles were assessed using immersion cell apparatus.

中文翻译：

---

抗氧化剂2,3-二氯，5,8-二羟基，1,4-萘醌抑制乙酰胆碱酯酶活性和淀粉样β42聚集体：用于治疗阿尔茨海默氏病的双重靶标治疗性候选化合物。

阿尔茨海默氏病的特征在于淀粉样蛋白β聚集和胆碱能神经退行性变。在本研究中，首次检测了纯DDN（2,3-二氯-5,8-二羟基-1,4-萘醌）作为乙酰胆碱酯酶（AChE）和_Aβ42聚集抑制剂的双重潜力。DDN在体外具有较高的抗氧化潜力，从而鼓励了这种研究。确实，它显示出有趣的抗氧化剂活性，对于ABTS和降低功率，其IC ₅₀值分别为9.8和4.3 µM。DDN抵抗_Aβ42聚集的能力通过thioflavine‐T分析进行了评估。强烈抑制_Aβ42在25 µM处测得的聚集超过90％。此外，结果表明DDN抑制了AChE（IC ₅₀ = 14.5 µM）。为了更好地理解DDN和AChE之间的相互作用，进行了分子对接。获得的数据预测，与加兰他敏（阳性对照）相比，高相互作用的特征在于在TYR337处的氢键键合。类似地，涉及AChE疏水相互作用的几个残基也暗示了该结构域与DDN的结合（ASP74，THR83和TYR124）。如果DDN无法通过血脑屏障，那么所有这些数据将毫无用处。因此，将DDN装入藻酸盐微球中以增强其稳定性和生物利用度。此后，使用浸没池装置评估药物释放曲线。