Discovery of novel dual-active 3-(4-(dimethylamino)phenyl)-7-aminoalcoxy-coumarin as potent and selective acetylcholinesterase inhibitor and antioxidant.

ABSTRACT: 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.

SUBMITTER: de Souza GA 

PROVIDER: S-EPMC6366430 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature