title: Synthesis of monomeric derivatives to probe memoquin's bivalent interactions.
abstract: Eight monomeric congeners, related to the multitarget lead candidate memoquin, were prepared and evaluated at multiple targets to determine their profile against Alzheimer's disease. 2-4 bind to AChE with similar low nanomolar affinities and function as effective inhibitors of amyloid aggregation. The most potent monovalent ligand 2 also inhibits BACE-1 in vitro and APP metabolism in primary chicken telencephalic neurons.
authors: Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. marialaura.bolognesi@unibo.it
authors: Maria Laura
authors: ML
authors: Bolognesi
authors: GianPaolo
authors: G
authors: Chiriano
authors: Manuela
authors: M
authors: Bartolini
authors: Francesca
authors: F
authors: Mancini
authors: Giovanni
authors: G
authors: Bottegoni
authors: Valentina
authors: V
authors: Maestri
authors: Stefan
authors: S
authors: Czvitkovich
authors: Manfred
authors: M
authors: Windisch
authors: Andrea
authors: A
authors: Cavalli
authors: Anna
authors: A
authors: Minarini
authors: Michela
authors: M
authors: Rosini
authors: Vincenzo
authors: V
authors: Tumiatti
authors: Vincenza
authors: V
authors: Andrisano
authors: Carlo
authors: C
authors: Melchiorre
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry; D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002091:Butyrylcholinesterase / Q000737:chemistry; D020134:Catalytic Domain; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005021:Ethylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D000473:Alkanes; D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D005021:Ethylamines; D008024:Ligands; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C521476:memoquin; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D053829:Amyloid Precursor Protein Secretases