Design, synthesis and evaluation of 4′-OH-flurbiprofen-chalcone hybrids as potential multifunctional agents for Alzheimer's disease treatment

被引：56

作者：

Cao, Zhongcheng ^{[1
]}

Yang, Jie ^{[1
]}

Xu, Rui ^{[1
]}

Song, Qin ^{[1
]}

Zhang, Xiaoyu ^{[1
]}

Liu, Hongyan ^{[1
]}

Qiang, Xiaoming ^{[1
]}

Li, Yan ^{[1
]}

Tan, Zhenghuai ^{[2
]}

Deng, Yong ^{[1
]}

机构：

[1] Sichuan Univ, West China Sch Pharm, Key Lab Drug Targeting & Drug Delivery Syst, Educ Minist,Dept Med Chem, 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 / 05期

关键词：

Alzheimer's disease; Flurbiprofen-chalcone hybrids; Multifunctional agents; Monoamine oxidase inhibitors; A beta aggregation inhibitors; Anti-inflammatory agents; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BETA-AMYLOID PLAQUES; MONOAMINE-OXIDASE; BIOLOGICAL EVALUATION; MAO-B; DERIVATIVES; INHIBITORS; FLURBIPROFEN; ANTIOXIDANT; ASSAY;

D O I：

10.1016/j.bmc.2018.01.030

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 4'-OH-flurbiprofen-chalcone hybrids were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The biological screening results indicated that most of these hybrids exhibited good multifunctional activities. Among them, compounds 7k and 7m demonstrated the best inhibitory effects on self-induced A beta(1-42) aggregation (60.0% and 78.2%, respectively) and Cu2+-induced A beta(1-42) aggregation (52.4% and 95.0%, respectively). Moreover, these two representative compounds also exhibited good antioxidant activities, MAO inhibitions, biometal chelating abilities and anti-neuroinflammatory activities in vitro. Furthermore, compound 7m displayed appropriate blood-brain barrier permeability. These multifunctional properties highlight compound 7k and 7m as promising candidates for further development of multi-functional drugs against AD. (C) 2018 Elsevier Ltd. All rights reserved.

引用

页码：1102 / 1115

页数：14

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