Detección in silico de fitomoléculas con potenciales actividades inhibitorias de Nucleolinas (NCL)
DOI:
https://doi.org/10.56152/StevianaFacenV14N1A2_2022Palabras clave:
Acoplamiento molecular, Fitomoléculas, Inhibidores, NucleolinaResumen
Las nucleolinas son proteínas localizadas generalmente en el núcleo celular, citoplasma y la superficie de las membranas cumpliendo funciones imprescindibles para la fisiología celular. Sin embargo, su mal funcionamiento se encuentra íntimamente relacionado con muchos tipos de cáncer, por lo que pueden ser consideradas como proteínas dianas para la búsqueda de moléculas con potencial inhibitorio con la finalidad de desarrollar nuevas estrategias para combatir al cáncer. Esta investigación tuvo como objetivos detectar fitoconstituyentes que presenten afinidades de interacción por el dominio de unión al ARN (DUA) de las nucleolinas y caracterizar dichas interacciones proteína-ligando mediante el análisis del acoplamiento molecular. Se preseleccionaron quince fitomoléculas con diferentes actividades biológicas para su estudio y se determinó el índice de drogabilidad del dominio DUA de las nucleolinas, las cuales presentaron un valor de 0,80 siendo altamente drogable. Posteriormente, se realizaron las pruebas de acoplamiento molecular entre los fitoconstituyentes seleccionados y la nucleolina. Los datos obtenidos en los ensayos de acoplamiento molecular evidenciaron que los fitoconstituyentes que presentaron mayor afinidad de interacción in silico fueron los triterpenos Maytenina, Taraxerol, Cucurbitacina B y Pristimerina, los cuales demostraron valores de energías libre de interacción (ΔG) iguales a -10,80±0,03 kcal.mol-1, -10,58±0,14 kcal.mol-1, -9,58±0,12 kcal.mol-1 y -9,48±0,35 kcal.mol-1 respectivamente. Los residuos involucrados activamente en las interacciones con las biomoléculas estabilizando la formación de la estructura de los complejos proteína-ligando fueron Asn100, Tyr103, Tyr134 y Arg158. Los hallazgos sugieren que dichos triterpenos podrían actuar como potenciales inhibidores de las nucleolinas debido a las afinidades manifestadas, sin embargo, estos resultados necesitan ser confirmados mediante ensayos in vitro e in vivo.
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