title: Synthesis and evaluation of novel rutaecarpine derivatives and related alkaloids derivatives as selective acetylcholinesterase inhibitors.
abstract: A series of novel rutaecarpine derivatives and related alkaloid derivatives 3-aminoalkanamido-substituted rutaecarpine 4a-f and 7,8-dehydrorutaecarpine 5a-c, and 6-aminoalkanamido-substituted 3-[2-(3-Indolyl)ethyl]-4(3a)-quinazolinones 8a-c, were synthesized and subjected to pharmacological evaluation as acetylcholinesterase (AChE) inhibitors. The synthetic compounds 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, Waihuan East Road 132, Guangzhou 510006, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Yi-Chi
authors.initials: YC
authors.lastname: Mai
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
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 / Q000187:drug effects; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D052999:Quinazolinones
chemical_list: D000110:Acetylcholinesterase; D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D026121:Indole Alkaloids; D011799:Quinazolines; C028632:rutecarpine; D052999:Quinazolinones