Molecular modeling and structural analysis of some tetrahydroindazole and cyclopentanepyrazole derivatives as COX-2 inhibitors

Efraín Polo-Cuadrado, Karen Acosta-Quiroga, Cristian Rojas-Peña, Yeray A. Rodriguez-Nuñez, Yorley Duarte, Iván Brito, Jonathan Cisterna, Margarita Gutiérrez

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

Resumen

In an attempt to rationalize the search for new potential anti-inflammatory compounds on the COX-2 enzyme, we carried out an in silico protocol that successfully combines the prediction of physicochemical and pharmacokinetic properties, molecular docking, molecular dynamic simulation, and free energy calculation. Starting from a small library of compounds synthesized previously, it was found that 70% of the compounds analyzed satisfy with the associated values to physicochemical principles as key evaluation parameters for the drug-likeness; all the compounds presented good gastrointestinal absorption and cerebral permeability and they showed an interaction with the Arg 106 residue of the COX-2 isoenzyme. Finally, it was obtained that compound 3ab has a binding mode, binding energy, and stability in the active site of COX-2 like the reference drug celecoxib, suggesting that this compound could become a powerful candidate in the inhibition of the COX-2 enzyme. In addition, we realized the crystallographic analysis of compounds 3j, 3r, and 3t defining the crystal parameters and the Packing interactions.

Idioma originalInglés
Número de artículo103540
PublicaciónArabian Journal of Chemistry
Volumen15
N.º2
DOI
EstadoPublicada - feb. 2022

Áreas temáticas de ASJC Scopus

  • Química (todo)
  • Ingeniería química (todo)

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