Crystal structure, quantum chemical insights, and molecular docking studies of Naryl-2-(N-disubstituted) acetamide compounds: potential inhibitors for neurodegenerative enzymes
The increase in and concern about neurodegenerative diseases continue to grow in an increasingly long-lived world population. Therefore, the search for new drugs continues to be a priority for medicinal chemistry. We present here the synthesis of a series of compounds with acetamide nuclei. Their st...
- Autores:
-
Camargo-Ayala, Lorena
Bedoya, Mauricio
Prent-Peñaloza, Luis
Polo-Cuadrado, Efraín
Osorio Lopez, Edison Humberto
Brito, Iván
Delgado, Gerzon E.
González, Wendy
Gutierrez, Margarita
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2024
- Institución:
- Universidad de Ibagué
- Repositorio:
- Repositorio Universidad de Ibagué
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.unibague.edu.co:20.500.12313/5800
- Acceso en línea:
- https://hdl.handle.net/20.500.12313/5800
https://pubs.rsc.org/en/content/articlelanding/2024/ra/d3ra08649f
- Palabra clave:
- Estructura cristalina
Binding energy
Crystal structure
Free energy
Neurodegenerative diseases
Quantum chemistry
- Rights
- openAccess
- License
- © 2024 The Royal Society of Chemistry.
| Summary: | The increase in and concern about neurodegenerative diseases continue to grow in an increasingly long-lived world population. Therefore, the search for new drugs continues to be a priority for medicinal chemistry. We present here the synthesis of a series of compounds with acetamide nuclei. Their structures were established using UV-Visible, NMR, HRMS and IR techniques. Furthermore, we report the crystal structures that were obtained from compounds 5a-5d by X-ray diffraction. The compounds were evaluated as potential inhibitors of the monoxidase enzymes; A (MAO-A) and B (MAO-B), and cholinesterases; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) through in silico studies using the induced fit docking (IFD) method and binding free energy (ΔGbind) calculations by the MMGBSA method. Interestingly, compounds 5b, 5c and 5d showed much better ΔGbind than the reference drug Zonisamide. Compound 5c is the best in the series, which indicates a potential selective affinity of our compounds against MAO-B, which could be a promising finding in the search for new drugs for Parkinson's disease treatment. The acetamide crystal exhibits moderate NLO properties suggesting that it could be considered a potential candidate for application in nonlinear optical devices. |
|---|