Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase Inhibitors.
Molecules
; 27(10)2022 May 13.
Article
en En
| MEDLINE
| ID: mdl-35630613
ABSTRACT
Acetylcholinesterase (AChE) is one of the classical targets in the treatment of Alzheimer's disease (AD). Inhibition of AChE slows down the hydrolysis of acetycholine and increases choline levels, improving the cognitive function. The achieved success of plant-based natural drugs acting as AChE inhibitors, such as galantamine (GAL) from Galanthus genus and huperzine A from Huperzia serrate (approved drug in China), in the treatment of AD, and the fact that natural compounds (NCs) are considered as safer and less toxic compared to synthetic drugs, led us to screen the available NCs (almost 150,000) in the ZINC12 database for AChE inhibitory activity. The compounds were screened virtually by molecular docking, filtered for suitable ADME properties, and 32 ligands from 23 structural groups were selected. The stability of the complexes was estimated via 1 µs molecular dynamics simulation. Ten compounds formed stable complexes with the enzyme and had a vendor and a reasonable price per mg. They were tested for AChE inhibitory and antioxidant activity. Five compounds showed weak AChE inhibition and three of them exhibited high antioxidant activity.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de la Colinesterasa
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Enfermedad de Alzheimer
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
Molecules
Asunto de la revista:
BIOLOGIA
Año:
2022
Tipo del documento:
Article