title: From AChE to BACE1 inhibitors: The role of the amine on the indanone scaffold.
abstract: In recent years, a progressive increase in age-related disorders could be observed in most western countries, among which Alzheimer's disease (AD) is one of the most challenging. BACE1 could be seen as an attractive target to develop disease-modifying compounds, and in this context, a new series of hybrid molecules was designed and synthesized, based on a previously identified multitarget lead compound. In particular, the amino side chain was appropriately modified to fit BACE1 as additional target. In vitro testing results pointed out compound 8 (IC50=2.49±0.08 μM), bearing the bulky bis(4-fluorophenyl)methyl)piperazine substituent, as the most potent BACE1 inhibitor of the series.
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, via Belmeloro 6, 40126 Bologna, Italy. Electronic address: angela.rampa@unibo.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Rampa
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancini
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: De Simone
authors.affiliation: Unit of Drug Discovery and Development, Italian Institute of Technology, via Morego 30, 16163 Genova, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Falchi
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Belluti
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Rita Maria Concetta
authors.initials: RM
authors.lastname: Di Martino
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gobbi
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Andrisano
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tarozzi
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Bartolini
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, via Belmeloro 6, 40126 Bologna, Italy; Unit of Drug Discovery and Development, Italian Institute of Technology, via Morego 30, 16163 Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bisi
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000588:Amines / Q000737:chemistry; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D007189:Indans / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D002800:Cholinesterase Inhibitors; D007189:Indans; D011480:Protease Inhibitors; C013352:indacrinone; D000110:Acetylcholinesterase; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: AChE; Alzheimer’s disease; BACE1; Drug discovery; Indanone