title: Inhibition of acetylcholinesterase, beta-amyloid aggregation, and NMDA receptors in Alzheimer's disease: a promising direction for the multi-target-directed ligands gold rush.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Alma Mater Studiorum, UniVersity of Bologna, Via Belmeloro 6, I-40126 Bologna, Italy. michela.rosini@unibo.it
authors.forename: Michela
authors.initials: M
authors.lastname: Rosini
authors.forename: Elena
authors.initials: E
authors.lastname: Simoni
authors.forename: Manuela
authors.initials: M
authors.lastname: Bartolini
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Luisa
authors.initials: L
authors.lastname: Ceccarini
authors.forename: Nicoleta
authors.initials: N
authors.lastname: Pascu
authors.forename: David W
authors.initials: DW
authors.lastname: McClymont
authors.forename: Andrea
authors.initials: A
authors.lastname: Tarozzi
authors.forename: Maria L
authors.initials: ML
authors.lastname: Bolognesi
authors.forename: Anna
authors.initials: A
authors.lastname: Minarini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tumiatti
authors.forename: Vincenza
authors.initials: V
authors.lastname: Andrisano
authors.forename: Ian R
authors.initials: IR
authors.lastname: Mellor
authors.forename: Carlo
authors.initials: C
authors.lastname: Melchiorre
mesh_terms: 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
chemical_list: D000682:Amyloid; D002800:Cholinesterase Inhibitors; D008024:Ligands; D016194:Receptors, N-Methyl-D-Aspartate; D000110:Acetylcholinesterase