title: Novel aromatic-polyamine conjugates as cholinesterase inhibitors with notable selectivity toward butyrylcholinesterase.
abstract: Three types of aromatic-polyamine conjugates (6a-6s) were designed, synthesized and evaluated as potential inhibitors for cholinesterases (ChEs). The results showed that anthraquinone-polyamine conjugates (AQPCs) exhibited the most potent acetylcholinesterase (AChE) inhibitory activity with IC50 values from 1.50 to 11.13 μM. Anthracene-polyamine conjugates (APCs) showed a surprising selectivity (from 76- to 3125-fold) and were most potent at inhibiting butyrylcholinesterase (BChE), with IC50 values from 0.016 to 0.657 μM. A Lineweaver-Burk plot and molecular modeling studies indicated that the representative compounds, 6l and 6k, targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of ChEs. Furthermore, APCs did not affect HepG2 cell viability at the concentration of 100 μM. Consequently, these polyamine conjugates could be thoroughly and systematically studied for the treatment of AD.
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Hong
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, People's Republic of China. Electronic address: luowen83@henu.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Luo
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yao
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, People's Republic of China.
authors.forename: Ya-Bin
authors.initials: YB
authors.lastname: Su
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, People's Republic of China.
authors.forename: Run-Guo
authors.initials: RG
authors.lastname: Tian
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, People's Republic of China. Electronic address: wcjsxq@henu.edu.cn.
authors.forename: Chao-Jie
authors.initials: CJ
authors.lastname: Wang
mesh_terms: D000081:Acetamides / Q000737:chemistry / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D016229:Amyloid beta-Peptides; D000873:Anthracenes / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry*; D020134:Catalytic Domain; D049109:Cell Proliferation / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D056945:Hep G2 Cells; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011073:Polyamines / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: C000600999:2-(4-aminobutylamino)-N-(anthracen-9-yl)acetamide hydrochloride; C000600998:2-(6-aminohexylamino)-N-(anthracen-9-yl)acetamide hydrochloride; D000081:Acetamides; D016229:Amyloid beta-Peptides; D000873:Anthracenes; D002800:Cholinesterase Inhibitors; D011073:Polyamines; D002091:Butyrylcholinesterase; C034020:anthracene
keywords: Acetylcholinesterase; Alzheimer’s disease; Butyrylcholinesterase; Polyamine conjugates