title: Aurone Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-β-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer's disease.
abstract: A series of aurone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compound 7d exhibited outstanding inhibitory activity for RatAChE, EeAChE and HuAChE (IC50= 0.00878 ± 0.0002 μM, 0.0212 ± 0.006 μM and 0.0371 ± 0.004 μM, respectively). Moreover, 7d displayed high antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. In addition, 7d also showed biometal chelating abilities, good self- and Cu2+-induced Aβ1-42aggregation inhibitory potency and high BBB permeability. These multifunctional properties highlight 7d as promising candidate for further studies directed to the development of novel drugs against AD.
authors.affiliation: 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.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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.forename: Xiaoming
authors.initials: X
authors.lastname: Qiang
authors.affiliation: 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.forename: Li
authors.initials: L
authors.lastname: Luo
authors.affiliation: 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.forename: Xia
authors.initials: X
authors.lastname: Yang
authors.affiliation: 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.forename: Ganyuan
authors.initials: G
authors.lastname: Xiao
authors.affiliation: Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan academy of Chinese Medicine Sciences, Chengdu, 610041, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan academy of Chinese Medicine Sciences, Chengdu, 610041, China.
authors.forename: Jiachen
authors.initials: J
authors.lastname: Ai
authors.affiliation: Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan academy of Chinese Medicine Sciences, Chengdu, 610041, China. Electronic address: tanzhh616@163.com.
authors.forename: Zhenghuai
authors.initials: Z
authors.lastname: Tan
authors.affiliation: 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.forename: Yong
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D004593:Electrophorus; D006801:Humans; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D008352:Mannich Bases; D018696:Neuroprotective Agents
keywords: Acetylcholinesterase inhibitors; Alzheimer's disease; Aurone Mannich base derivatives; Aβ aggregation inhibitors; Multifunctional agents