Design, synthesis and molecular modeling of isothiochromanone derivatives as acetylcholinesterase inhibitors

被引：6

作者：

Shuai, Wen ^{[1
,2
]}

Li, Wenlong ^{[1
,2
]}

Yin, Ying ^{[1
,2
]}

Yang, Limei ^{[1
,2
]}

Xu, Feijie ^{[1
,2
]}

Xu, Shengtao ^{[1
,2
]}

Yao, Hequan ^{[1
,2
]}

Zhu, Zheying ^{[3
]}

Xu, Jinyi ^{[1
,2
]}

机构：

[1] China Pharmaceut Univ, State Key Lab Nat Med, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, Peoples R China

[2] China Pharmaceut Univ, Dept Med Chem, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, Peoples R China

[3] Univ Nottingham, Sch Pharm, Div Mol Therapeut & Formulat, Univ Pk Campus, Nottingham NG7 2RD, England

来源：

FUTURE MEDICINAL CHEMISTRY | 2019年 / 11卷 / 20期

基金：

中国国家自然科学基金;

关键词：

acetylcholinesterase inhibitor; Alzheimer's disease; dual binding site; isoselenochromanone; isothiochromanone; BENZYL PYRIDINIUM MOIETY; ALZHEIMERS-DISEASE; BIOLOGICAL EVALUATION; HYBRIDS; DONEPEZIL; POTENT; DOCKING;

D O I：

10.4155/fmc-2019-0125

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Aim: A series of novel isothio- and isoselenochromanone derivatives bearing N-benzyl pyridinium moiety were designed, synthesized and evaluated as acetylcholinesterase (AChE) inhibitors. Results: Most of the target compounds exhibited potent anti-AChE activities with IC50 values in nanomolar ranges. Among them, compound 15a exhibited the most potent anti-AChE activity (IC50 = 2.7 nM), moderate antioxidant activity and low neurotoxicity. Moreover, the kinetic and docking studies revealed that compound 15a was a mixed-type inhibitor, which bounds to peripheral anionic site and catalytic active site of AChE. Conclusion: Those results suggested that compound 15a might be a potential candidate for AD treatment. [GRAPHICS] .

引用

页码：2687 / 2699

页数：13

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