Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Journal of enzyme inhibition and medicinal chemistry, 2019-01, Vol.34 (1), p.631-637

Ort / Verlag

England: Taylor & Francis

Erscheinungsjahr

2019

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.