Chalcones are considered effective templates for the development of monoamine oxidase (MAO) and cholinesterase (ChE) inhibitors. The present work describes the syntheses of selected 1,3‐benzodioxine‐containing chalcones (CD3, CD8 and CD10), and their inhibitory activities against MAO‐A, MAO‐B, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). Compound CD8 most potently inhibited MAO‐B with an IC₅₀ value of 0.026 μM, followed by CD10 and CD3 (1.54 and 1.68 μM, respectively). CD8 potently and non‐selectively inhibited MAO‐A (IC₅₀ value of 0.023 μM). On the other hand, CD10 and CD8 inhibited AChE with IC₅₀ values of 5.40 and 9.57 μM, respectively. Kinetics and reversibility experiments showed that all synthesized molecules were competitive and reversible inhibitors, and the K_i values of CD8 for MAO‐A and MAO‐B were 0.018 and 0.0019 μM, respectively. By in vitro and in silico analyses, all compounds were found to have high passive human gastrointestinal absorptions, blood‐brain barrier permeabilities, and non‐toxicities. Molecular docking simulations revealed that docking affinity of each compound for MAO‐B was higher than that for MAO‐A. The results indicate that CD8 is a potent non‐selective MAO inhibitor, and CD10 is an effective selective MAO‐B inhibitor, and both possess AChE inhibitory activity. Therefore, we suggest that CD8 and CD10 be considered potential dual‐targeting inhibitors of MAO and AChE for the treatment of various neurodegenerative disorders.

中文翻译：

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选择含 1,3-苯并二恶英的查耳酮作为多效单胺氧化酶和乙酰​​胆碱酯酶抑制剂。

查耳酮被认为是开发单胺氧化酶 (MAO) 和胆碱酯酶 (ChE) 抑制剂的有效模板。目前的工作描述了选定的含 1,3-苯并二恶英的查耳酮（CD3、CD8和CD10）的合成，以及它们对 MAO-A、MAO-B、乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BChE) 的抑制活性。化合物CD8最有效地抑制 MAO-B，IC ₅₀值为 0.026 μM，其次是CD10和CD3（分别为 1.54 和 1.68 μM）。CD8有效且非选择性地抑制 MAO-A（IC ₅₀值为 0.023 μM）。另一方面，CD10和CD8抑制 AChE，IC ₅₀值分别为 5.40 和 9.57 μM。动力学和可逆性实验表明，所有合成的分子都是竞争性和可逆性抑制剂，CD8对 MAO-A 和 MAO-B的 K _i值分别为 0.018 和 0.0019 μM。通过体外和计算机分析，发现所有化合物都具有高被动人体胃肠吸收、血脑屏障渗透性和无毒性。分子对接模拟表明，每种化合物对 MAO-B 的对接亲和力高于对 MAO-A 的对接亲和力。结果表明CD8是一种有效的非选择性 MAO 抑制剂，CD10是一种有效的选择性 MAO-B 抑制剂，两者都具有 AChE 抑制活性。因此，我们建议将CD8和CD10视为潜在的 MAO 和 AChE 双重靶向抑制剂，用于治疗各种神经退行性疾病。