title: [Design, synthesis and cholinesterase inhibitory activity of quinoline-polyamine conjugates].
abstract: A series of quinoline-polyamine conjugates (8a-8n) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs). Some of these compounds had potent ChEs inhibitory activity with IC50 values at micromolar range. Compound 8n exhibited the strongest inhibition on acetylcholinesterase (AChE) with an IC50 value of 8.78 micromol x L(-1), and compound 8i showed the most potent inhibition on butyrylcholinesterase (BChE) with IC50 value of 1.60 micromol x L(-1) which was slightly better than rivastigmine. The structure-activity relationship revealed that the chain length of polyamine and linker played important roles for inhibitory activity. Molecular modeling studies showed that 8i targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of cholinesterases.
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: Kai
authors.initials: K
authors.lastname: Huang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Hong
authors.forename: Chao-Jie
authors.initials: CJ
authors.lastname: Wang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D020128:Inhibitory Concentration 50; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D011073:Polyamines; D011804:Quinolines; C037219:quinoline; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase