In silico identification of AChE and PARP-1 dual-targeted inhibitors of Alzheimer's disease.
J Mol Model
; 24(7): 151, 2018 Jun 05.
Article
en En
| MEDLINE
| ID: mdl-29869722
ABSTRACT
Alzheimer's disease (AD) is a chronic neurodegenerative disease of the elderly that seriously affects the quality of life and the life expectancy of those affected. There is, as yet, no effective drug treatment of AD, although several acetylcholinesterase (AChE) inhibitors and a glutamate antagonist can provide relief from its symptoms. Recent studies have indicated that the overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) may promote nerve cell death in the brains of AD patients, implying that PARP-1 inhibition may have therapeutic value for the treatment of AD. Therefore, it is important to investigate novel agents with both AChE- and PARP-1-inhibitory bioactivities. In this study, the structure-based virtual screening of PARP-1 inhibitors was performed to search for potential agents with high affinities for AChE. The dynamic stability of the selected AChE-ligand complexes was investigated by molecular dynamics (MD) simulation. Two compounds, CID57390505 and CID71605390, showed high affinities for and stability in complex with AChE in docking and MD simulations. Thus, our in silico research identified two compounds with AChE and PARP-1 dual-targeted activities, indicating that this technique could aid attempts to develop more potent agents against AD.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Acetilcolinesterasa
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Inhibidores de la Colinesterasa
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Inhibidores Enzimáticos
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Simulación de Dinámica Molecular
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Simulación del Acoplamiento Molecular
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Poli(ADP-Ribosa) Polimerasa-1
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article