title: Design, synthesis and biological evaluation of D-ring opened galantamine analogs as multifunctional anti-Alzheimer agents.
abstract: Facing the multifactorial nature of Alzheimer's disease, twelve dibenzofuran/carbazole derivatives, which can be considered as the D-ring opened analogs of galantamine, have been designed and synthesized as multifunctional anti-Alzheimer agents. In vitro tests revealed that compounds 3 and 5, which bear a nitrate moiety in the molecule, showed a potent inhibition activity towards AChE and compound 3 showed a good Aβ42 aggregation inhibitory activity. Moreover, 3 and 5 could also release a relative low concentration of NO in vitro and they did not show toxicity to neuronal cells, while exerted a neuroprotective effect against the Aβ-induced toxicity. More importantly, compound 3 showed a significant spatial memory improving effect in vivo, and a good safety in the ex vivo toxicity study.
authors.affiliation: Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, Pharmaceutical Research Center, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, Pharmaceutical Research Center, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China.
authors.forename: Xubin
authors.initials: X
authors.lastname: Fang
authors.affiliation: Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, Pharmaceutical Research Center, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China. Electronic address: sgou@seu.edu.cn.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gou
authors.affiliation: Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Amelie
authors.initials: A
authors.lastname: Lupp
authors.affiliation: Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Lenhardt
authors.affiliation: Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, Pharmaceutical Research Center, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Zhangjian
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Institute of Pharmacy, Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Jena, Germany. Electronic address: Fleck-Christian@t-online.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Fleck
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D015195:Drug Design; D005260:Female; D005702:Galantamine / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D002800:Cholinesterase Inhibitors; D005702:Galantamine; D009569:Nitric Oxide
keywords: AChE inhibitors; Anti-Alzheimer; Aβ aggregation inhibitors; Galantamine analogs; Neuroprotective agents