title: Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer's disease.
abstract: Neurodegeneration, a complex disease state, comprises several pathways that contribute to cell death. Conventional approach of targeting only one of these pathways has not been proven to be entirely successful and has demanded a hypothetical change as to how researchers design and develop new drugs. In this study, effects of a series of α, β-unsaturated carbonyl-based tetralone derivatives against Alzheimer's disease (AD) were investigated. Moreover, their activity toward amyloid β-induced cytotoxicity was also studied. Six compounds including 3f, 3o, 3u, 3ae, 3af, and 3ag were discovered to be most protective against Aβ-induced neuronal cell death in PC12 cells. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against MAO-B, AChE, and self-induced Aβ1-42aggregation. The compound 3f exhibited best AChE (IC50= 0.045 ± 0.02 μm) inhibitory potential in addition to potent inhibition of MAO-B (IC50= 0.88 ± 0.12 μm). Furthermore, compound 3f disassembled the Aβ fibrils produced by self-induced Aβ aggregation by 78.2 ± 4.8%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Leng
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China. qinhuali@whut.edu.cn.
authors.forename: Hua-Li
authors.initials: HL
authors.lastname: Qin
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China.
authors.forename: Kaicheng
authors.initials: K
authors.lastname: Zhu
authors.affiliation: Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Jantan
authors.affiliation: Department of Chemistry, University of Sargodha, Sargodha, Pakistan.
authors.forename: Muhammad Ajaz
authors.initials: MA
authors.lastname: Hussain
authors.affiliation: Department of Chemistry, University of Sargodha, Sargodha, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Sher
authors.affiliation: Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Muhammad Wahab
authors.initials: MW
authors.lastname: Amjad
authors.affiliation: Department of Chemistry, University of Sargodha, Sargodha, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Naeem-Ul-Hassan
authors.affiliation: Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Waqas
authors.initials: W
authors.lastname: Ahmad
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China. snab_hussaini@yahoo.com.|Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. snab_hussaini@yahoo.com.
authors.forename: Syed Nasir Abbas
authors.initials: SN
authors.lastname: Bukhari
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects; D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D002091:Butyrylcholinesterase / Q000187:drug effects; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000627:therapeutic use; D016716:PC12 Cells; D066244:Proton Magnetic Resonance Spectroscopy; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D044024:Tetralones / Q000627:therapeutic use*
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D044024:Tetralones; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: acetylcholinesterase; butyrylcholinesterase; monoamine oxidase; neurodegeneration; neuroprotection