设计并合成新型香豆素-吡啶鎓杂化物：体外乙酰胆碱酯酶抑制活性。
Design and synthesis of novel coumarin-pyridinium hybrids: In vitro cholinesterase inhibitory activity.
机构信息
Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
出版信息
Bioorg Chem. 2018 Apr;77:311-319. doi: 10.1016/j.bioorg.2018.01.013. Epub 2018 Jan 31.
A novel series of coumarin-pyridinium hybrids were synthesized and evaluated as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using Ellman's method. Among synthesized compounds, 1-(3-fluorobenzyl)-4-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium bromide (7l) was found to be the most active compound toward AChE (IC = 10.14 µM), 1-(3-chlorobenzyl)-3-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium bromide (7g) and 1-(2,3-dichlorobenzyl)-3-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium chloride (7h) depicted the best BChE inhibitory activity (ICs = 0.32 and 0.43 µM, respectively). Although most compounds showed moderate to good anti-AChE activity, their anti-BChE activity was more significant and compound 7g was found as the most selective BChE with SI of 101.18. Also, kinetic study of the compounds 7g and 7l displayed a mixed type inhibition for both AChE and BChE. Furthermore, they were evaluated against β-secretase; however, they showed low inhibitory activity.
合成了一系列新型香豆素-吡啶鎓杂化物，并采用 Ellman 法评价其对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的抑制作用。在所合成的化合物中，1-（3-氟苄基）-4-（（2-氧代-2H-色烯-3-羧酰胺基）甲基）吡啶溴化物（7l）对 AChE 的抑制活性最强（IC=10.14 µM），1-（3-氯苄基）-3-（（2-氧代-2H-色烯-3-羧酰胺基）甲基）吡啶溴化物（7g）和 1-（2,3-二氯苄基）-3-（（2-氧代-2H-色烯-3-羧酰胺基）甲基）吡啶氯化物（7h）对 BChE 的抑制活性最好（ICs=0.32 和 0.43 µM）。虽然大多数化合物表现出中等至良好的抗 AChE 活性，但它们的抗 BChE 活性更为显著，化合物 7g 被发现是最具选择性的 BChE，其选择性指数为 101.18。此外，化合物 7g 和 7l 的动力学研究显示它们对 AChE 和 BChE 均表现出混合型抑制。此外，它们还被评估了对β-分泌酶的抑制作用，但显示出较低的抑制活性。
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