Molecular modeling and structural analysis of some tetrahydroindazole and cyclopentanepyrazole derivatives as COX-2 inhibitors
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Fecha
2022-02
Profesor/a Guía
Facultad/escuela
Idioma
en
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Editor
Elsevier B.V.
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Licencia CC
Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
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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.
Notas
Indexación: Scopus.
Palabras clave
COX-2 enzyme, Crystal structure, Molecular Docking, Molecular dynamics simulation, Pyrazole, Tetrahydroindazole
Citación
Arabian Journal of Chemistry, Volume 15, Issue 2, February 2022, Article number 103540
DOI
10.1016/j.arabjc.2021.103540