title: [Design, synthesis and evaluation of tacrine-methoxybenzene hybrids as cholinesterases inhibitors].
abstract: A series of tacrine-methoxybenzene hybrids (5a-5i) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs). All the compounds had better ChEs inhibitory activities than tacrine with IC50 values at the nanomolar range. Compound 5h exhibited the strongest inhibition on acetylcholinesterase (AChE) with an IC50 value of 6.74 nmol x L(-1) and compound 5f showed the most potent inhibition on butyrylcholinesterase with IC50 value of 3.83 nmol x L(-1). Kinetic and molecular modeling studies showed that these hybrids targeted both the catalytic active site and the peripheral anionic site of AChE.
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, China. luowen83@henu.edu.cn
authors.forename: Wen
authors.initials: W
authors.lastname: Luo
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Zhao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ya-Bin
authors.initials: YB
authors.lastname: Su
authors.forename: Chao-Jie
authors.initials: CJ
authors.lastname: Wang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000840:Anisoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000378:metabolism*; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D020128:Inhibitory Concentration 50; D013619:Tacrine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000840:Anisoles; D002800:Cholinesterase Inhibitors; D013619:Tacrine; C060998:anisole; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase