title: Synthesis and acetylcholinesterase and butyrylcholinesterase inhibitory activities of 7-alkoxyl substituted indolizinoquinoline-5,12-dione derivatives.
abstract: A series of novel 7-alkoxyl substituted indolizinoquinoline-5,12-dione derivatives were synthesized. The cholinesterase inhibition assays indicated that most synthesized compounds exhibited good activity for acetylcholinesterase (AChE) and high selectivity index of AChE over butyrylcholinesterase (BuChE). Compound 12b exhibited the most potent AChE inhibitory activity with an IC(50)  value of 0.068 µM and the highest selectivity index of 144. Kinetic study of AChE indicated that a mixed type of inhibition pattern existed for these indolizinoquinoline-5,12-dione derivatives. Molecular docking study indicated that compound 12b could bind to both the catalytically active site and the peripheral anionic site of AChE.
authors: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Zu-Ping
authors: ZP
authors: Wu
authors: Xi-Wei
authors: XW
authors: Wu
authors: Ting
authors: T
authors: Shen
authors: Yan-Ping
authors: YP
authors: Li
authors: Xi
authors: X
authors: Cheng
authors: Lian-Quan
authors: LQ
authors: Gu
authors: Zhi-Shu
authors: ZS
authors: Huang
authors: Lin-Kun
authors: LK
authors: An
mesh_terms: D000110:Acetylcholinesterase; D001665:Binding Sites; D002091:Butyrylcholinesterase; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007212:Indolizines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D007212:Indolizines; D011804:Quinolines; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase