Título

A Computational Method for the Binding Mode Prediction of COX-1 and COX-2 Inhibitors: Analyzing the Union of Coxibs, Oxicams, Propionic and Acetic Acids

Autor

ESTEFANY BELLO VARGAS

JOSE MARIO ORDOÑEZ PALACIOS

Nivel de Acceso

Acceso Abierto

Licencia

http://creativecommons.org/licenses/by/4.0

Identificador alterno

issn/1424-8247

Materias

BIOLOGÍA Y QUÍMICA - (CTI) QUÍMICA - (CTI) anti-inflammatory, cyclooxygenase (COXs), molecular docking, NSAIDs, Celecoxib, Meloxicam, Ibuprofen,

Resumen o descripción

Among the biological targets extensively investigated to improve inflammation and chronic inflammatory conditions, cyclooxygenase enzymes (COXs) occupy a prominent position. The inhibition of these enzymes, essential for mitigating inflammatory processes, is chiefly achieved through Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). In this work, we introduce a novel method—based on computational molecular docking—that could aid in the structure-based design of new compounds or the description of the anti-inflammatory activity of already-tested compounds. For this, we used eight crystal complexes (four COX-1 and COX-2 each), and each pair had a specific NSAID: Celecoxib, Meloxicam, Ibuprofen, and Indomethacin. This selection was based on the ligand selectivity towards COX-1 or COX-2 and their binding mode. An interaction profile of each NSAID was compiled to detect the residues that are key for their binding mode, highlighting the interaction made by the Me group. Furthermore, we rigorously validated our models based on structural accuracy (RMSD < 1) and (R2 > 70) using eight NSAIDs and thirteen compounds with IC50 values for each enzyme. Therefore, this model can be used for the binding mode prediction of small and structurally rigid compounds that work as COX inhibitors or the prediction of new compounds that are designed by means of a structure-based approach.

Editor

MDPI Open Access Journals

Fecha de publicación

2023

Tipo de publicación

Artículo

Recurso de información

http://riaa.uaem.mx/handle/20.500.12055/4266

1424-8247

Formato

pdf

Idioma

Inglés

Relación

Pharmaceuticals

12

16

https://www.mdpi.com/1424-8247/16/12/1688

Cobertura

MEX

Audiencia

Investigadores

Repositorio Orígen

Repositorio Institucional de Acceso Abierto de la Universidad Autónoma del Estado de Morelos

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