College of Pharmaceutical Science, Government T.D. Medical College, Alappuzha, India.
Organic Chemistry Division, SAS, VIT University, Vellore, India.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):188-197. doi: 10.1080/14756366.2020.1842390.
Nine compounds () containing the morpholine moiety were assessed for their inhibitory activities against monoamine oxidases (MAOs) and acetylcholinesterase (AChE). Most of the compounds potently inhibited MAO-B; most potently inhibited with an IC value of 0.030 µM, followed by (0.25 µM). most potently inhibited AChE (IC = 6.1 µM), followed by (IC = 12.01 µM) and most potently inhibited MAO-A (IC = 7.1 µM). was a reversible mixed-type inhibitor of MAO-B ( = 0.018 µM); reversibly competitively inhibited AChE ( = 2.52 µM); and reversibly noncompetitively inhibited AChE ( = 7.04 µM). , and crossed the blood-brain barrier, and were non-toxic to normal VERO cells. These results show that is a selective inhibitor of MAO-B and that is a dual-acting inhibitor of AChE and MAO-B, and that both should be considered candidates for the treatment of Alzheimer's disease.
研究了九种含有吗啉结构的化合物对单胺氧化酶（MAO）和乙酰胆碱酯酶（AChE）的抑制活性。大多数化合物对 MAO-B 具有很强的抑制作用；对 MAO-B 的抑制作用最强，IC 值为 0.030 μM，其次是（0.25 μM）。对 AChE 的抑制作用最强（IC = 6.1 μM），其次是（IC = 12.01 μM）和对 MAO-A 的抑制作用最强（IC = 7.1 μM）。是 MAO-B 的可逆混合型抑制剂（= 0.018 μM）；可逆竞争性抑制 AChE（= 2.52 μM）；和可逆非竞争性抑制 AChE（= 7.04 μM）。 、 和 能透过血脑屏障，对正常 VERO 细胞无毒性。这些结果表明， 是 MAO-B 的选择性抑制剂， 是 AChE 和 MAO-B 的双重作用抑制剂，两者都应被视为治疗阿尔茨海默病的候选药物。
