title: Ferulic acid-carbazole hybrid compounds: Combination of cholinesterase inhibition, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents.
abstract: In order to search for novel multifunctional anti-Alzheimer agents, a series of ferulic acid-carbazole hybrid compounds were designed and synthesized. Ellman's assay revealed that the hybrid compounds showed moderate to potent inhibitory activity against the cholinesterases. Particularly, the AChE inhibition potency of compound 5k (IC50 1.9μM) was even 5-fold higher than that of galantamine. In addition, the target compounds showed pronounced antioxidant ability and neuroprotective property, especially against the ROS-induced toxicity. Notably, the neuroprotective effect of 5k was obviously superior to that of the mixture of ferulic acid and carbazole, indicating the therapeutic effect of the hybrid compound is better than the combination administration of the corresponding mixture.
authors.affiliation: Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
authors.forename: Mohao
authors.initials: M
authors.lastname: Chen
authors.affiliation: Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
authors.forename: Xubin
authors.initials: X
authors.lastname: Fang
authors.affiliation: Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China. Electronic address: sgou@seu.edu.cn.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gou
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: chenliduo12@gmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors; D002227:Carbazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D003373:Coumaric Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D015195:Drug Design; D004593:Electrophorus; D005702:Galantamine / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010851:Picrates / Q000037:antagonists & inhibitors; D011485:Protein Binding; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001713:Biphenyl Compounds; D002227:Carbazoles; D002800:Cholinesterase Inhibitors; D003373:Coumaric Acids; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010851:Picrates; C075222:amyloid beta-protein (1-42); D005702:Galantamine; C004999:ferulic acid; D006861:Hydrogen Peroxide; C004931:1,1-diphenyl-2-picrylhydrazyl; D000110:Acetylcholinesterase
keywords: AChE inhibitor; Anti-Alzheimer; Antioxidant; Hybrid compounds