title: Synthesis and screening for antiacetylcholinesterase activity of (1-benzyl-4-oxopiperidin-3-ylidene)methylindoles and -pyrroles related to donepezil.
abstract: The design, synthesis, and rapid evaluation of a new class of acetylcholinesterase (AChE) inhibitors related to donepezil are reported. A molecular dynamics simulation of the complex between AChE and one representative compound of the series showed a possible inhibitor binding mode in which favorable interactions are formed between the benzylpiperidinone moiety and some active-site residues. The biochemical evaluation of this newly synthesized series was performed using a chemiluminescent method suitable for high-throughput screening.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy. aldoandr@alma.unibo.it
authors.forename: A
authors.initials: A
authors.lastname: Andreani
authors.forename: A
authors.initials: A
authors.lastname: Cavalli
authors.forename: M
authors.initials: M
authors.lastname: Granaiola
authors.forename: M
authors.initials: M
authors.lastname: Guardigli
authors.forename: A
authors.initials: A
authors.lastname: Leoni
authors.forename: A
authors.initials: A
authors.lastname: Locatelli
authors.forename: R
authors.initials: R
authors.lastname: Morigi
authors.forename: M
authors.initials: M
authors.lastname: Rambaldi
authors.forename: M
authors.initials: M
authors.lastname: Recanatini
authors.forename: A
authors.initials: A
authors.lastname: Roda
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D000077265:Donepezil; D004353:Drug Evaluation, Preclinical; D007189:Indans / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D008163:Luminescent Measurements; D008958:Models, Molecular; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D007189:Indans; D007211:Indoles; D018697:Nootropic Agents; D010880:Piperidines; D011758:Pyrroles; D000077265:Donepezil; D000110:Acetylcholinesterase