Inhibition of acetylcholinesterase, beta-amyloid aggregation, and NMDA receptors in Alzheimer's disease: a promising direction for the multi-target-directed ligands gold rush.
Alzheimer's disease (AD) is a multifactorial syndrome with several target proteins contributing to its etiology. To confront AD, an innovative strategy is to design single chemical entities able to simultaneously modulate more than one target. Here, we present compounds that inhibit acetylcholinesterase and NMDA receptor activity. Furthermore, these compounds inhibit AChE-induced Abeta aggregation and display antioxidant properties, emerging as lead candidates for treating AD.
Rosini
Michela
M
Department of Pharmaceutical Sciences, Alma Mater Studiorum, UniVersity of Bologna, Via Belmeloro 6, I-40126 Bologna, Italy. michela.rosini@unibo.it
Simoni
Elena
E
Bartolini
Manuela
M
Cavalli
Andrea
A
Ceccarini
Luisa
L
Pascu
Nicoleta
N
McClymont
David W
DW
Tarozzi
Andrea
A
Bolognesi
Maria L
ML
Minarini
Anna
A
Tumiatti
Vincenzo
V
Andrisano
Vincenza
V
Mellor
Ian R
IR
Melchiorre
Carlo
C
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000682:Amyloid; D002800:Cholinesterase Inhibitors; D008024:Ligands; D016194:Receptors, N-Methyl-D-Aspartate; D000110:Acetylcholinesterase