title: Synthesis and evaluation of 4-hydroxyl aurone derivatives as multifunctional agents for the treatment of Alzheimer's disease.
abstract: A series of 4-hydroxyl aurone derivatives were designed synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The results demonstrated that most of the derivatives exhibited good multifunctional properties. Among them, compound 14e displayed good inhibitory activities of self- and Cu(2+)-induced Aβ1-42 aggregation with 99.2% and 84.0% at 25μM, respectively, and high antioxidant activity with a value 1.90-fold of Trolox. In addition, 14e also showed remarkable inhibitory activities of both monoamine oxidase A and B with IC50 values of 0.271μM and 0.393μM, respectively. However the 6-methoxyl aurones 15a-c revealed excellent selectivity toward MAO-B. Furthermore, the representative compounds 14e and 15b displayed good metal-chelating abilities and blood-brain barrier (BBB) permeabilities in vitro.
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: Yuxing
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: 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. 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* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000378:metabolism; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003300:Copper / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066329:Protein Aggregates / Q000187:drug effects; D013552:Swine
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001572:Benzofurans; D002614:Chelating Agents; D008996:Monoamine Oxidase Inhibitors; D010446:Peptide Fragments; D066329:Protein Aggregates; C075222:amyloid beta-protein (1-42); C486837:aurone; D003300:Copper; D008995:Monoamine Oxidase
keywords: Alzheimer’s disease; Aurone derivatives; Monoamine oxidase; Multifunctional agents; β-Amyloid aggregation