Extensive SAR and computational studies of 3-{4-[(benzylmethylamino)methyl]phenyl}-6,7-dimethoxy-2H-2-chromenone (AP2238) derivatives.
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.
Piazzi
Lorna
L
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. lorna.piazzi@unibo.it
Cavalli
Andrea
A
Belluti
Federica
F
Bisi
Alessandra
A
Gobbi
Silvia
S
Rizzo
Stefano
S
Bartolini
Manuela
M
Andrisano
Vincenza
V
Recanatini
Maurizio
M
Rampa
Angela
A
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
C475423:AP 2238; D001596:Benzylamines; D002800:Cholinesterase Inhibitors; D003374:Coumarins; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase