Biomedicines · 2021 · 11 citations · 31 references
PharmacyMedicinal ChemistryPharmacologyDrug DiscoveryLead OptimizationNeuropharmacologyHit-to-lead OptimizationLead Compound DesignLead DiscoveryPotency OptimizationSelectivity OptimizationStructure-activity Relationship AnalysisMedicinal Chemistry ApplicationsMonoamine Oxidase InhibitionMonoamine Oxidase InhibitorsPotency PredictionReversible Enzyme InhibitionReversible InhibitionSelectivity Index OptimizationStructure - Activity Relationship Optimization
A series of dietary flavonoid acacetin 7-O-methyl ether derivatives were computationally designed aiming to improve the selectivity and potency profiles against monoamine oxidase (MAO) B. The designed compounds were evaluated for their potential to inhibit human MAO-A and -B. Compounds 1c, 2c, 3c, and 4c were the most potent with a Ki of 37 to 68 nM against MAO-B. Compounds 1c–4c displayed more than a thousand-fold selectivity index towards MAO-B compared with MAO-A. Moreover, compounds 1c and 2c showed reversible inhibition of MAO-B. These results provide a basis for further studies on the potential application of these modified flavonoids for the treatment of Parkinson’s Disease and other neurological disorders.
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