Design, synthesis and evaluation of novel 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease

doi:10.1016/j.bmcl.2015.02.015

科研成果详情

题名	Design, synthesis and evaluation of novel 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease
作者	Liao, Shixian1; Deng, Hui1; Huang, Shengbin1; Yang, Jingyuan1; Wang, Siqian1; Yin, Baodi 1; Zheng, Tieli1; Zhang, Dafeng1; Liu, Jinsong1; Gao, Guohui2; Ma, Jianfeng1; Deng, Zhennan1
发表日期	2015-04-01
发表期刊	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Alzheimer's disease Hybrids Cholinesterase inhibitors Antioxidant A beta(1-42) aggregation inhibition Neuroprotectant
其他关键词	MULTITARGETED COMPOUNDS ; DERIVATIVES ; ACETYLCHOLINESTERASE ; ANTIOXIDANT ; STRATEGIES ; INHIBITORS
摘要	A series of 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that the target compounds exhibited good acetylcholinesterase (AChE) inhibitory potencies, high selectivity toward AChE over butyrylcholinesterase (BuChE), potential antioxidant activities and significant inhibitory potencies of self-induced beta-amyloid peptide (A beta) aggregation. In particular, compound 14c had the strongest AChE inhibitory activity with IC50 value of 12.8 nM, potent inhibition of self-induced A beta(1-42) aggregation with inhibition ratio of 33.8% at 25 mu M. Moreover, compound 14c acted as an antioxidant, as well as a neuroprotectant. Furthermore, 14c could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 14c might be a potential multifunctional candidate for the treatment of AD. (C) 2015 Elsevier Ltd. All rights reserved.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81100782]; Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province [Y2110400]; Health Bureaue of Zhejiang Province [2012KYA128]; Wenzhou Municipal Science and Technology Bureau Foundation of China [Y20140112]
出版者	PERGAMON-ELSEVIER SCIENCE LTD
出版地	OXFORD
ISSN	0960-894X
EISSN	1464-3405
卷号	25 期号:7 页码:1541-1545
DOI	10.1016/j.bmcl.2015.02.015
页数	5
WOS类目	Chemistry, Medicinal ; Chemistry, Organic
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
WOS记录号	WOS:000351688700035
收录类别	SCIE ; PUBMED ; SCOPUS ; IC
URL	查看原文
PubMed ID	25724825
SCOPUSEID	2-s2.0-84925514007
通讯作者地址	[Ma, Jianfeng]School and Hospital of Stomatology,Wenzhou Medical University,Wenzhou,325027,China
Scopus学科分类	Biochemistry;Molecular Medicine;Molecular Biology;Pharmaceutical Science;Drug Discovery;Clinical Biochemistry;Organic Chemistry
引用统计	被引频次：19[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/18900
专题	口腔医学院、附属口腔医院检验医学院（生命科学学院、生物学实验教学中心）
通讯作者	Ma, Jianfeng
作者单位	1.School and Hospital of Stomatology,Wenzhou Medical University,Wenzhou,325027,China; 2.School of Laboratory Medicine and Life Science,Wenzhou Medical University,Wenzhou,325027,China
第一作者单位	口腔医学院、附属口腔医院
通讯作者单位	口腔医学院、附属口腔医院
第一作者的第一单位	口腔医学院、附属口腔医院
推荐引用方式 GB/T 7714	Liao, Shixian,Deng, Hui,Huang, Shengbin,et al. Design, synthesis and evaluation of novel 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2015,25(7):1541-1545.
APA	Liao, Shixian., Deng, Hui., Huang, Shengbin., Yang, Jingyuan., Wang, Siqian., ... & Deng, Zhennan. (2015). Design, synthesis and evaluation of novel 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 25(7), 1541-1545.
MLA	Liao, Shixian,et al."Design, synthesis and evaluation of novel 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 25.7(2015):1541-1545.