Discovery of novel dual-active 3-(4-(dimethylamino)phenyl)-7-aminoalcoxy-coumarin as potent and selective acetylcholinesterase inhibitor and antioxidant
Copyright policy )Discovery of novel dual-active 3-(4-(dimethylamino)phenyl)-7-aminoalcoxy-coumarin as potent and selective acetylcholinesterase inhibitor and antioxidant
A series of 3-substituted-7-aminoalcoxy-coumarin was designed and evaluated as cholinesterase inhibitors and antioxidants. All compounds were effective in inhibiting AChE with potencies in the nanomolar range. The 3-(4-(dimethylamino)phenyl)-7-aminoethoxy-coumarin (6a) was considered a hit, showing good AChE inhibition potency (IC50 = 20 nM) and selectivity (IC50 BuChE/AChE = 354), quite similar to the reference drug donepezil (IC50 = 6 nM; IC50 BuChE/AChE = 365), also presenting antioxidant properties, low citotoxicity and good-predicted ADMET properties. The mode of action (mixed-type) and SAR analysis for this series of compounds were described by means of kinetic and molecular modeling evaluations.
Models, Molecular, antioxidant, cholinesterase, Cell Survival, Short Communication, RM1-950, Antioxidants, Mice, Structure-Activity Relationship, Coumarins, Drug Discovery, Tumor Cells, Cultured, Animals, Horses, coumarins, Dose-Response Relationship, Drug, Molecular Structure, Butyrylcholinesterase, Electrophorus, Acetylcholinesterase, Therapeutics. Pharmacology, Cholinesterase Inhibitors, bioisosterism
Models, Molecular, antioxidant, cholinesterase, Cell Survival, Short Communication, RM1-950, Antioxidants, Mice, Structure-Activity Relationship, Coumarins, Drug Discovery, Tumor Cells, Cultured, Animals, Horses, coumarins, Dose-Response Relationship, Drug, Molecular Structure, Butyrylcholinesterase, Electrophorus, Acetylcholinesterase, Therapeutics. Pharmacology, Cholinesterase Inhibitors, bioisosterism
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