title: Bis-huperzine B: highly potent and selective acetylcholinesterase inhibitors.
abstract: By targeting dual active sites of AChE, a series of bis-huperzine B analogues with various lengths of the tether were designed, synthesized, and tested for their inhibition and selectivity. The most potent bis-huperzine B (5g) exhibited 3900-fold increase in AChE inhibition and 930-fold greater in selectivity for AChE vs BuChE than its parent huperzine B.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Zhangjiang, 201203, Shanghai.
authors.forename: Song
authors.initials: S
authors.lastname: Feng
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Wang
authors.forename: Xuchang
authors.initials: X
authors.lastname: He
authors.forename: Suxin
authors.initials: S
authors.lastname: Zheng
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Xican
authors.initials: X
authors.lastname: Tang
authors.forename: Donglu
authors.initials: D
authors.lastname: Bai
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry; D000470:Alkaloids / Q000737:chemistry; D000818:Animals; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002091:Butyrylcholinesterase / Q000737:chemistry; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D029542:Lycopodiaceae; D008958:Models, Molecular; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D001952:Bridged-Ring Compounds; D002800:Cholinesterase Inhibitors; D011728:Pyridones; C497146:bis(18)-huperzine B; C053016:huperzine B; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase