丁酰胆碱酯酶
化学
乙酰胆碱酯酶
阿切
胆碱酯酶
多奈哌齐
IC50型
立体化学
吗啉
哌啶
效力
胺气处理
酶
对接(动物)
药理学
生物化学
体外
药物化学
有机化学
护理部
病理
疾病
痴呆
医学
作者
Abol-Hassan Etemadi,Salar Hemmati,Mohammad Shahrivar-Gargari,Yasaman Tamaddon Abibiglue,Ahad Bavili,Maryam Hamzeh-Mivehroud,Siavoush Dastmalchi
标识
DOI:10.1002/cbdv.202300075
摘要
Abstract Indanone derivatives containing meta/para‐substituted aminopropoxy benzyl/benzylidene moieties were designed based on the structures of donepezil and ebselen analogs as the cholinesterase inhibitors. The designed compounds were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were measured. Inhibitory potencies (IC 50 values) for the synthesized compounds ranged from 0.12 to 11.92 μM and 0.04 to 24.36 μM against AChE and BChE, respectively. Compound 5 c showed the highest AChE inhibitory potency with IC 50 value of 0.12 μM, whereas the highest BChE inhibition was achieved by structure 7 b (IC 50 =0.04 μM). Structure‐activity relationship (SAR) analysis revealed that there is no significant difference between meta and para ‐substituted derivatives in AChE and BChE inhibition. However, the most potent AChE inhibitor 5 c belongs to meta‐substituted compounds, while the most active BChE inhibitor is para‐substituted derivative 7 b . The order of enzyme inhibition potency based on the substituted amine group is dimethyl amine>piperidine>morpholine. Compounds containing C=C linkage are more potent AChE inhibitors than the corresponding saturated structures. Molecular docking studies indicated that 5 c interacts with AChE in a very similar way to that observed experimentally for donepezil. The introduced indanone‐aminopropoxy benzylidenes could be used in drug‐discovery against Alzheimer's disease.
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