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...

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Detalles Bibliográficos
Autores principales: de Souza, Gabriela Alves, da Silva, Soraia John, Del Cistia, Catarina de Nigris, Pitasse-Santos, Paulo, Pires, Lucas de Oliveira, Passos, Yulli Moraes, Cordeiro, Yraima, Cardoso, Cristiane Martins, Castro, Rosane Nora, Sant’Anna, Carlos Mauricio R., Kümmerle, Arthur Eugen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Short Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366430/
https://www.ncbi.nlm.nih.gov/pubmed/30727776
http://dx.doi.org/10.1080/14756366.2019.1571270
Descripción
Sumario: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(50) = 20 nM) and selectivity (IC(50) BuChE/AChE = 354), quite similar to the reference drug donepezil (IC(50) = 6 nM; IC(50) 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.

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