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

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 energ...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Efraín Polo-Cuadrado, Karen Acosta-Quiroga, Cristian Rojas-Peña, Yeray A. Rodriguez-Nuñez, Yorley Duarte, Iván Brito, Jonathan Cisterna, Margarita Gutiérrez
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Tetrahydroindazole Pyrazole COX-2 enzyme Molecular Docking Molecular dynamics simulation Crystal structure Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/952489a82d76454395357642e8a66aa5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:952489a82d76454395357642e8a66aa5
record_format	dspace
spelling	oai:doaj.org-article:952489a82d76454395357642e8a66aa52021-12-04T04:33:29ZMolecular modeling and structural analysis of some tetrahydroindazole and cyclopentanepyrazole derivatives as COX-2 inhibitors1878-535210.1016/j.arabjc.2021.103540https://doaj.org/article/952489a82d76454395357642e8a66aa52022-02-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1878535221005554https://doaj.org/toc/1878-5352In 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.Efraín Polo-CuadradoKaren Acosta-QuirogaCristian Rojas-PeñaYeray A. Rodriguez-NuñezYorley DuarteIván BritoJonathan CisternaMargarita GutiérrezElsevierarticleTetrahydroindazolePyrazoleCOX-2 enzymeMolecular DockingMolecular dynamics simulationCrystal structureChemistryQD1-999ENArabian Journal of Chemistry, Vol 15, Iss 2, Pp 103540- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Tetrahydroindazole Pyrazole COX-2 enzyme Molecular Docking Molecular dynamics simulation Crystal structure Chemistry QD1-999
spellingShingle	Tetrahydroindazole Pyrazole COX-2 enzyme Molecular Docking Molecular dynamics simulation Crystal structure Chemistry QD1-999 Efraín Polo-Cuadrado Karen Acosta-Quiroga Cristian Rojas-Peña Yeray A. Rodriguez-Nuñez Yorley Duarte Iván Brito Jonathan Cisterna Margarita Gutiérrez Molecular modeling and structural analysis of some tetrahydroindazole and cyclopentanepyrazole derivatives as COX-2 inhibitors
description	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.
format	article
author	Efraín Polo-Cuadrado Karen Acosta-Quiroga Cristian Rojas-Peña Yeray A. Rodriguez-Nuñez Yorley Duarte Iván Brito Jonathan Cisterna Margarita Gutiérrez
author_facet	Efraín Polo-Cuadrado Karen Acosta-Quiroga Cristian Rojas-Peña Yeray A. Rodriguez-Nuñez Yorley Duarte Iván Brito Jonathan Cisterna Margarita Gutiérrez
author_sort	Efraín Polo-Cuadrado
title	Molecular modeling and structural analysis of some tetrahydroindazole and cyclopentanepyrazole derivatives as COX-2 inhibitors
title_short	Molecular modeling and structural analysis of some tetrahydroindazole and cyclopentanepyrazole derivatives as COX-2 inhibitors
title_full	Molecular modeling and structural analysis of some tetrahydroindazole and cyclopentanepyrazole derivatives as COX-2 inhibitors
title_fullStr	Molecular modeling and structural analysis of some tetrahydroindazole and cyclopentanepyrazole derivatives as COX-2 inhibitors
title_full_unstemmed	Molecular modeling and structural analysis of some tetrahydroindazole and cyclopentanepyrazole derivatives as COX-2 inhibitors
title_sort	molecular modeling and structural analysis of some tetrahydroindazole and cyclopentanepyrazole derivatives as cox-2 inhibitors
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/952489a82d76454395357642e8a66aa5
work_keys_str_mv	AT efrainpolocuadrado molecularmodelingandstructuralanalysisofsometetrahydroindazoleandcyclopentanepyrazolederivativesascox2inhibitors AT karenacostaquiroga molecularmodelingandstructuralanalysisofsometetrahydroindazoleandcyclopentanepyrazolederivativesascox2inhibitors AT cristianrojaspena molecularmodelingandstructuralanalysisofsometetrahydroindazoleandcyclopentanepyrazolederivativesascox2inhibitors AT yerayarodrigueznunez molecularmodelingandstructuralanalysisofsometetrahydroindazoleandcyclopentanepyrazolederivativesascox2inhibitors AT yorleyduarte molecularmodelingandstructuralanalysisofsometetrahydroindazoleandcyclopentanepyrazolederivativesascox2inhibitors AT ivanbrito molecularmodelingandstructuralanalysisofsometetrahydroindazoleandcyclopentanepyrazolederivativesascox2inhibitors AT jonathancisterna molecularmodelingandstructuralanalysisofsometetrahydroindazoleandcyclopentanepyrazolederivativesascox2inhibitors AT margaritagutierrez molecularmodelingandstructuralanalysisofsometetrahydroindazoleandcyclopentanepyrazolederivativesascox2inhibitors
_version_	1718372982674423808

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

Ejemplares similares