title: Design, Synthesis, and Biological Evaluation of a New Series of Biphenyl/Bibenzyl Derivatives Functioning as Dual Inhibitors of Acetylcholinesterase and Butyrylcholinesterase.
abstract: Alzheimer's disease (AD), the most common form of dementia in adults, is a progressive neurodegenerative disorder of the brain characterized by loss of memory and steady deterioration of cognition. Here, a series of symmetrical molecules containing biphenyl/bibenzyl scaffolds (12-36) were designed, synthesized, and evaluated for their ability to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A biological evaluation showed that most of these biphenyl derivatives were potent AChE and BuChE inhibitors. Among them, compound15displayed the greatest ability to inhibit BuChE (IC50= 0.74 µM) and was also a good AChE inhibitor (IC50= 1.18 µM). Compound19was not only a potent AChE inhibitor (IC50= 0.096 µM), but also a mild BuChE inhibitor (IC50=1.25 µM). Overall, these results suggested that compound19may be a promising agent in the treatment of AD.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines & Ministry of Health Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. wangdmchina@imm.ac.cn.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines & Ministry of Health Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. fengbo@imm.ac.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.affiliation: Beijing Institutes For Drug Control, Beijing 100050, China. Fuhuifree@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines & Ministry of Health Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. liuailin@imm.ac.cn.
authors.forename: Ai-Lin
authors.initials: AL
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines & Ministry of Health Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. wlin@imm.ac.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines & Ministry of Health Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. dugh@imm.ac.cn.
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Du
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines & Ministry of Health Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. ws@imm.ac.cn.
authors.forename: Song
authors.initials: S
authors.lastname: Wu
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D001632:Bibenzyls / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000110:Acetylcholinesterase; D001632:Bibenzyls; D001713:Biphenyl Compounds; D002091:Butyrylcholinesterase; D002800:Cholinesterase Inhibitors; C010574:biphenyl
keywords: Alzheimer’s disease; acetylcholinesterase inhibitors; biphenyl/bibenzyl derivatives; butyrylcholinesterase inhibitors; molecular docking