title: Quinones bearing non-steroidal anti-inflammatory fragments as multitarget ligands for Alzheimer's disease.
abstract: The anti-amyloid properties shared by several quinones inspired the design of a new series of hybrids derived from the multi-target drug candidate memoquin (1). The hybrids consist of a central benzoquinone core and a fragment taken from non-steroidal anti-inflammatory drugs, connected through polyamine linkers. The new hybrids retain the potent anti-aggregating activity of the parent 1, while exhibiting micromolar AChE inhibitory activities. Remarkably, 2, 4, (R)-6 and (S)-6 were Aβ aggregation inhibitors even more potent than 1. The balanced amyloid/cholinesterase inhibitory profile is an added value that makes the present series of compounds promising leads against Alzheimer's disease.
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy; Department of Drug Discovery and Development, Italian Institute of Technology, Via Morego 30, 16163 Genoa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Prati
authors.forename: Manuela
authors.initials: M
authors.lastname: Bartolini
authors.forename: Elena
authors.initials: E
authors.lastname: Simoni
authors.forename: Angela
authors.initials: A
authors.lastname: De Simone
authors.forename: Antonella
authors.initials: A
authors.lastname: Pinto
authors.forename: Vincenza
authors.initials: V
authors.lastname: Andrisano
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Bolognesi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000682:Amyloid / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D011809:Quinones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000682:Amyloid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002800:Cholinesterase Inhibitors; D008024:Ligands; D011809:Quinones
keywords: Acetylcholinesterase inhibitors; Alzheimer’s disease; Amyloid aggregation inhibitors; Memoquin; Non-steroidal anti-inflammatory drugs