Synthesis and screening for antiacetylcholinesterase activity of (1-benzyl-4-oxopiperidin-3-ylidene)methylindoles and -pyrroles related to donepezil.
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.
Andreani
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A
Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy. aldoandr@alma.unibo.it
Cavalli
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A
Granaiola
M
M
Guardigli
M
M
Leoni
A
A
Locatelli
A
A
Morigi
R
R
Rambaldi
M
M
Recanatini
M
M
Roda
A
A
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
D007189:Indans; D007211:Indoles; D018697:Nootropic Agents; D010880:Piperidines; D011758:Pyrroles; D000077265:Donepezil; D000110:Acetylcholinesterase