A series of 4-aminomethyl-7-benzyloxy-2H-chromen-2-ones was investigated with the aim of identifying multiple inhibitors of cholinesterases (acetyl- and butyryl-, AChE and BChE) and monoamine oxidase B (MAO B) as potential anti-Alzheimer molecules. Starting from a previously reported potent MAO B inhibitor (3), we studied single-point modifications at the benzyloxy or at the basic moiety. The in vitro screening highlighted triple-acting compounds (6, 8, 9, 16, 20) showing nanomolar and selective MAO B inhibition along with IC50 against ChEs at the low micromolar level. Enzyme kinetics analysis toward AChE and docking simulations on the target enzymes were run in order to get insight into the mechanism of action and plausible binding modes.

中文翻译：

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Chasing ChEs-MAO B Multi-Targeting 4-Aminomethyl-7-Benzyloxy-2H-Chromen-2-ones

研究了一系列 4-aminomethyl-7-benzyloxy-2H-chromen-2-ones，目的是确定胆碱酯酶（乙酰基和丁酰基、AChE 和 BChE）和单胺氧化酶 B（MAO B）的多种抑制剂作为潜在的抗阿尔茨海默病分子。从先前报道的有效 MAO B 抑制剂 (3) 开始，我们研究了苄氧基或碱性部分的单点修饰。体外筛选突出显示三重作用化合物（6、8、9、16、20）显示纳摩尔和选择性 MAO B 抑制以及在低微摩尔水平对 ChE 的 IC50。运行针对 AChE 的酶动力学分析和对目标酶的对接模拟，以深入了解作用机制和合理的结合模式。