title: Multi-target-directed coumarin derivatives: hAChE and BACE1 inhibitors as potential anti-Alzheimer compounds.
abstract: The complex etiology of Alzheimer's disease (AD) prompts scientists to develop multifunctional compounds to combat causes and symptoms of such neurodegeneration. To this aim we designed, synthesized, and tested a series of compounds by introducing halophenylalkylamidic functions on the scaffold of AP2238, which is a dual binding site acetylcholinesterase inhibitor. The inhibitory activity was successfully extended to the beta-site amyloid precursor protein cleavage enzyme, leading to the discovery of a potent inhibitor of this enzyme (3) and affording multifunctional compounds (2, 6, 8) for the treatment of AD.
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. lorna.piazzi@unibo.it
authors.forename: Lorna
authors.initials: L
authors.lastname: Piazzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Francesco
authors.initials: F
authors.lastname: Colizzi
authors.forename: Federica
authors.initials: F
authors.lastname: Belluti
authors.forename: Manuela
authors.initials: M
authors.lastname: Bartolini
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Recanatini
authors.forename: Vincenza
authors.initials: V
authors.lastname: Andrisano
authors.forename: Angela
authors.initials: A
authors.lastname: Rampa
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000577:Amides; D002800:Cholinesterase Inhibitors; D003374:Coumarins; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human