3-(4-[[Benzyl(methyl)amino]methyl]phenyl)-6,7-dimethoxy-2H-2-chromenone (AP2238) inhibits both acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation: a dual function lead for Alzheimer's disease therapy.
In recent years, the investigation of acetylcholinesterase (AChE) inhibitors has gained further interest, because the involvement of the peripheral site of the enzyme in the beta-amyloid (Abeta) aggregation process has been disclosed. We present here, for the first time, a direct evidence of the Abeta antiaggregating action of an AChE inhibitor (AP2238) purposely designed to bind at both the catalytic and the peripheral sites of the human enzyme.
Piazzi
Lorna
L
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, Italy.
Rampa
Angela
A
Bisi
Alessandra
A
Gobbi
Silvia
S
Belluti
Federica
F
Cavalli
Andrea
A
Bartolini
Manuela
M
Andrisano
Vincenza
V
Valenti
Piero
P
Recanatini
Maurizio
M
D000110:Acetylcholinesterase / Q000737:chemistry*; D000122:Acetylthiocholine / Q000737:chemistry; D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry; D001596:Benzylamines / Q000138:chemical synthesis* / Q000737:chemistry; D002091:Butyrylcholinesterase / Q000737:chemistry; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry; D005470:Fluorometry; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D013329:Structure-Activity Relationship
C475423:AP 2238; D016229:Amyloid beta-Peptides; D001578:Benzopyrans; D001596:Benzylamines; D002800:Cholinesterase Inhibitors; D003374:Coumarins; D000122:Acetylthiocholine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase