title: 2-(2-indolyl-)-4(3H)-quinazolines derivates as new inhibitors of AChE: design, synthesis, biological evaluation and molecular modelling.
abstract: We recently reported that synthetic derivatives of rutaecarpine alkaloid exhibited high acetyl cholinesterase (AChE) inhibitory activity and high selectivity for AChE over butyrylcholinesterases (BuChE). To explore novel effective drugs for the treatment of Alzheimer's disease (AD), in this paper, further research results were presented. Starting from a structure-based drug design, a series of novel 2-(2-indolyl-)-4(3H)-quinazolines derivates were designed and synthesized as the ring-opened analogues of rutaecarpine alkaloid and subjected to pharmacological evaluation as AChE inhibitors. Among them, derivates 3a-c and 3g-h exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by kinetic characterization and the molecular docking studies.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, P. R. China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Jin-Qiang
authors.initials: JQ
authors.lastname: Hou
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Huang
authors.forename: Tian-Miao
authors.initials: TM
authors.lastname: Ou
authors.forename: Jia-Heng
authors.initials: JH
authors.lastname: Tan
authors.forename: Lin-Kun
authors.initials: LK
authors.lastname: An
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.forename: Lian-Quan
authors.initials: LQ
authors.lastname: Gu
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D026121:Indole Alkaloids / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011799:Quinazolines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D052999:Quinazolinones
chemical_list: D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002800:Cholinesterase Inhibitors; D026121:Indole Alkaloids; D011799:Quinazolines; C028632:rutecarpine; D052999:Quinazolinones