title: Design, synthesis and evaluation of chromone-2-carboxamido-alkylbenzylamines as multifunctional agents for the treatment of Alzheimer's disease.
abstract: A series of chromone-2-carboxamido-alkylbenzylamines were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good multifunctional activities. Among them, compound 49 displayed excellent inhibitory potency toward acetylcholinesterase (AChE), moderate anti-oxidative activity, selective biometal chelating, and possessed good inhibitory effects on self-induced and Cu(2+)-induced Aβ aggregation. Both kinetic analysis of AChE inhibition and molecular modeling study indicated that 49 was a mixed-type inhibitor, binding simultaneously to the catalytic active site and peripheral anionic site of AChE. These results suggested that 49 might be a potential multifunctional agent for AD treatment.
authors: Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Qiang
authors: Q
authors: Liu
authors: Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Xiaoming
authors: X
authors: Qiang
authors: Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Yan
authors: Y
authors: Li
authors: Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Zhipei
authors: Z
authors: Sang
authors: Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Yuxing
authors: Y
authors: Li
authors: Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, China. Electronic address: tanzhh616@163.com.
authors: Zhenghuai
authors: Z
authors: Tan
authors: Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: dengyong@scu.edu.cn.
authors: Yong
authors: Y
authors: Deng
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D001596:Benzylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D002867:Chromones / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D062105:Molecular Docking Simulation
chemical_list: D000975:Antioxidants; D001596:Benzylamines; D002800:Cholinesterase Inhibitors; D002867:Chromones
keywords: Acetylcholinesterase inhibitors; Alzheimer’s disease; Anti-oxidative activity; Aβ aggregation inhibitors; Biometal chelators; Chromone-2-carboxamido-alkylbenzylamines