ChemMedChem · 2020 · 17 citations · 19 references
MedicineMedicinal ChemistryPharmacologyDrug DiscoveryNeurochemistryNeuropharmacologyEnzyme InhibitionLigand-based DesignMulti-target Drug DesignNeurodegenerative Disease PharmacologyNeuroprotectionNeuroprotective PharmacologyAlzheimer Disease NeuroprotectionChemical Structure-activity RelationshipsChemical Synthesis Of AnaloguesMedicinal Chemistry ApplicationsMonoamine Oxidase TargetsNeuroprotective AgentsNeuroprotective Drug DevelopmentReactive Oxygen Species Generation
Abstract A number of 1,2,3,4‐tetrahydrochromeno[3,2‐ c ]pyridin‐10‐one derivatives have been synthesized and screened against different targets involved in the onset and progression of Alzheimer's disease (AD), such as acetyl‐ and butyrylcholinesterase (AChE and BChE), monoamine oxidases A and B (MAO A and B), aggregation of β‐amyloid (Aβ) and reactive oxygen species (ROS) production. Derivatives 1 c , 3 b , 4 and 5 a showed multifaceted profiles of promising anti‐AD features and returned well‐balanced multitargeting inhibitory activities. Moreover, compound 1 f , a potent and selective human MAO B inhibitor (IC 50 =0.89 μM), proved to be a safe neuroprotectant in a human neuroblastoma cell line (SH‐SY5Y) by improving viability impaired by Aβ 1–42 and pro‐oxidant insult. Furthermore, structure–activity relationships (SARs) and docking models were derived in order to assist further hit‐to‐lead optimization stage.
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Rapid colorimetric assay for cell growth and survival
François Denizot, Rita Lang · Journal of Immunological Methods · 1986 · 4.9K citations