title: Extensive SAR and computational studies of 3-{4-[(benzylmethylamino)methyl]phenyl}-6,7-dimethoxy-2H-2-chromenone (AP2238) derivatives.
abstract: AP2238 was the first compound published to bind both anionic sites of the human acetylcholinesterase, allowing the simultaneous inhibition of the catalytic and the amyloid-beta pro-aggregating activities of AChE. Here we attempted to derive a comprehensive structure-activity relationship picture for this molecule, affording 28 derivatives for which AChE and BChE inhibitory activities were evaluated. Selected compounds were also tested for their ability to prevent the AChE-induced Abeta-aggregation. Moreover, docking simulations and molecular orbital calculations were performed.
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. lorna.piazzi@unibo.it
authors.forename: Lorna
authors.initials: L
authors.lastname: Piazzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Federica
authors.initials: F
authors.lastname: Belluti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bisi
authors.forename: Silvia
authors.initials: S
authors.lastname: Gobbi
authors.forename: Stefano
authors.initials: S
authors.lastname: Rizzo
authors.forename: Manuela
authors.initials: M
authors.lastname: Bartolini
authors.forename: Vincenza
authors.initials: V
authors.lastname: Andrisano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Recanatini
authors.forename: Angela
authors.initials: A
authors.lastname: Rampa
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry; D001596:Benzylamines / Q000138:chemical synthesis* / Q000737:chemistry; D002091:Butyrylcholinesterase / Q000737:chemistry; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D003198:Computer Simulation; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: C475423:AP 2238; D001596:Benzylamines; D002800:Cholinesterase Inhibitors; D003374:Coumarins; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase