Multifunctional 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives with acetylcholinesterase, monoamine oxidases and β-amyloid aggregation inhibitory activities as potential agents against Alzheimer's disease

被引：21

作者：

Xu, Rui ^{[1
]}

Xiao, Ganyuan ^{[1
]}

Li, Yan ^{[1
]}

Liu, Hongyan ^{[1
]}

Song, Qing ^{[1
]}

Zhang, Xiaoyu ^{[1
]}

Yang, Ziyi ^{[1
]}

Zheng, Yunxiaozhu ^{[1
]}

Tan, Zhenghuai ^{[2
]}

Deng, Yong ^{[1
]}

机构：

[1] Sichuan Univ, West China Sch Pharm, Key Lab Drug Targeting & Drug Delivery Syst, Dept Med Chem,Educ Minist, Chengdu 610041, Sichuan, Peoples R China

[2] Sichuan Acad Chinese Med Sci, Inst Tradit Chinese Med Pharmacol & Toxicol, Chengdu 610041, Sichuan, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2018年 / 26卷 / 08期

关键词：

Alzheimer's disease; Benzo[d]isothiazol-3(2H)-one derivatives; Monoamine oxidase inhibitors; Acetylcholinesterase inhibitors; A beta aggregation inhibitors; Multifunctional agents; TARGET-DIRECTED LIGANDS; MANNICH BASE DERIVATIVES; NEUROPROTECTIVE PROPERTIES; BIOLOGICAL EVALUATION; OXIDATIVE STRESS; DESIGN; HYBRIDS; ANTIOXIDANT; DRUGS; ASSAY;

D O I：

10.1016/j.bmc.2018.02.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro assays indicated that most of these derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compounds 11b and 11d displayed comprehensive advantages, with good AChE (IC50 = 0.29 +/- 0.01 mu M and 0.46 +/- 0.02 mu M, respectively), MAO-A (IC50 = 8.2 +/- 0.08 mu M and 7.9 +/- 0.07 mu M, respectively) and MAO-B (IC50 = 20.1 +/- 0.16 mu M and 43.8 +/- 2.0% at 10 mu M, respectively) inhibitory activities, moderate self-induced A beta(1-42) aggregation inhibitory potency (35.4 +/- 0.42% and 48.0 +/- 1.53% at 25 mu M, respectively) and potential antioxidant activity. In addition, the two representative compounds displayed high BBB permeability in vitro. Taken together, these multifunctional properties make 11b and 11d as a promising candidate for the development of efficient drugs against AD. (C) 2018 Elsevier Ltd. All rights reserved.

引用

页码：1885 / 1895

页数：11

共 45 条

[11] Multitarget-Directed Benzylideneindanone Derivatives: Anti-β-Amyloid (Aβ) Aggregation, Antioxidant, Metal Chelation, and Monoamine Oxidase B (MAO-B) Inhibition Properties against Alzheimer's Disease [J].