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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

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

de Souza Gabriela Alves GA   da Silva Soraia John SJ   Del Cistia Catarina de Nigris CN   Pitasse-Santos Paulo P   Pires Lucas de Oliveira LO   Passos Yulli Moraes YM   Cordeiro Yraima Y   Cardoso Cristiane Martins CM   Castro Rosane Nora RN   Sant'Anna Carlos Mauricio R CMR   Kümmerle Arthur Eugen AE  

Journal of enzyme inhibition and medicinal chemistry 20191201 1

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 (IC<sub>50</sub> = 20 nM) and selectivity (IC<sub>50</sub> BuChE/AChE = 354), quite similar to the reference drug donepezil (IC<sub>50</sub> = 6 nM; IC<sub>50</sub> BuChE/  ...[more]

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