title: Design, synthesis and evaluation of 2-arylethenyl-N-methylquinolinium derivatives as effective multifunctional agents for Alzheimer's disease treatment.
abstract: A series of 2-arylethenyl-N-methylquinolinium derivatives were designed and synthesized based on our previous research of 2-arylethenylquinoline analogues as multifunctional agents for the treatment of Alzheimer's disease (AD) (Eur. J. Med. Chem. 2015, 89, 349-361). The results of in vitro biological activity evaluation, including β-amyloid (Aβ) aggregation inhibition, cholinesterase inhibition, and antioxidant activity, showed that introduction of N-methyl in quinoline ring significantly improved the anti-AD potential of compounds. The optimal compound, compound a12, dramatically attenuated the cell death of glutamate-induced HT22 cells by preventing the generation of ROS and increasing the level of GSH. Most importantly, intragastric administration of a12•HAc was well tolerated at doses up to 2000 mg/kg and could traverse blood-brain barrier.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Xia
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Qian-Liang
authors.initials: QL
authors.lastname: Guo
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Zhen-Quan
authors.initials: ZQ
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Jia-Qiang
authors.initials: JQ
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Tian-Miao
authors.initials: TM
authors.lastname: Ou
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Jia-Heng
authors.initials: JH
authors.lastname: Tan
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Hong-Gen
authors.initials: HG
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China. Electronic address: ceshzs@mail.sysu.edu.cn.
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000187:drug effects; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000737:chemistry; D015195:Drug Design; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D011804:Quinolines; D017382:Reactive Oxygen Species; C037219:quinoline; D005978:Glutathione
keywords: 2-arylethenyl-N-methylquinolinium derivatives; Alzheimer's disease; Aβ aggregation; Cholinesterase inhibition; Neuroprotection