info:eu-repo/semantics/article
Synthesis, biological evaluation and molecular modeling studies of substitutedN-benzyl-2-phenylethanamines as cholinesterase inhibitors
Fecha
2020-06Registro en:
Carmona Viglianco, Maria Florencia; Zaragoza Puchol, José Daniel; Parravicini, Oscar; Garro, Adriana; Enriz, Ricardo Daniel; et al.; Synthesis, biological evaluation and molecular modeling studies of substitutedN-benzyl-2-phenylethanamines as cholinesterase inhibitors; Royal Society of Chemistry; New Journal of Chemistry; 44; 22; 6-2020; 9466-9476
1144-0546
1369-9261
CONICET Digital
CONICET
Autor
Carmona Viglianco, Maria Florencia
Zaragoza Puchol, José Daniel
Parravicini, Oscar
Garro, Adriana
Enriz, Ricardo Daniel
Feresin, Gabriela Egly
Kurina Sanz, Marcela Beatriz
Orden, Alejandro Agustin
Resumen
In this work, we report the synthesis of a series of derivatives of N-benzyl-2-phenylethanamine which is the framework of norbelladine, the natural common precursor of the Amaryllidaceae alkaloids. These compounds were assessed in the inhibition of both AChE and BChE which are the enzymes responsible for the breakdown of acetylcholine and hence they constitute targets in the palliative treatment of Alzheimer's disease. In particular, brominated derivatives exhibited the lowest IC50 values against AChE. Interestingly, the presence of iodine in one of the aromatic rings highly increased the inhibition of BChE compared to its analogues, with an IC50 value similar to that of galantamine, which is the reference compound currently used in the treatment of AD. A possible mechanism of action for these compounds was determined by molecular modeling studies using combined techniques of docking and molecular dynamics simulations.