title: Rational design and synthesis of highly potent anti-acetylcholinesterase activity huperzine A derivatives.
abstract: By targeting multi-active sites of acetylcholinesterase (AChE), a series of huperzine A (Hup A) derivatives with various aromatic ring groups were designed and synthesized by Schiff reaction. They were evaluated as AChE and butyrylcholinesterase (BChE) inhibitors. Results showed very significant specificity that the group of imine derivatives could inhibit TcAChE and hAChE, but no inhibitory effect on hBChE was detected. The experiment was explained by a docking study. In the docking model, we confirmed that aromatic ring of Hup A derivatives played the pi-pi stacking against aminophenol residues of AChE, and the structure-activity relationship (SAR) was discussed.
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, The Chinese Academy of Sciences, Kunming 650204, PR China. yanjian@scbg.ac.cn
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Lirong
authors.initials: L
authors.lastname: Sun
authors.forename: Guisheng
authors.initials: G
authors.lastname: Wu
authors.forename: Ping
authors.initials: P
authors.lastname: Yi
authors.forename: Fumei
authors.initials: F
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Xianmin
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhongrong
authors.initials: Z
authors.lastname: Li
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Yang
authors.forename: Huairong
authors.initials: H
authors.lastname: Luo
authors.forename: Minghua
authors.initials: M
authors.lastname: Qiu
mesh_terms: D000110:Acetylcholinesterase; D000470:Alkaloids; D002091:Butyrylcholinesterase; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D018696:Neuroprotective Agents / Q000138:chemical synthesis; D011485:Protein Binding; D012545:Schiff Bases / Q000737:chemistry; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D012545:Schiff Bases; D012717:Sesquiterpenes; C050426:huperzine A; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase