Evaluación in silico de flavonoides como potenciales inhibidores del fentanilo

La creciente preocupación por el uso del fentanilo, debido a su abuso y efectos adversos, subraya la necesidad urgente de encontrar alternativas terapéuticas más seguras. El objetivo general de esta investigación evaluar la interacción de metabolitos secundarios con el receptor opioide mu (Mor) y su...

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Autores:
Giraldo Muñoz, Ariany Yoaly
Tipo de recurso:
Trabajo de grado de pregrado
Fecha de publicación:
2024
Institución:
Universidad Distrital Francisco José de Caldas
Repositorio:
RIUD: repositorio U. Distrital
Idioma:
spa
OAI Identifier:
oai:repository.udistrital.edu.co:11349/41913
Acceso en línea:
http://hdl.handle.net/11349/41913
Palabra clave:
Fentanilo
Receptor opioide mu
Metabolitos secundarios
Acoplamiento molecular
Compuestos naturales.
Licenciatura en Biología -- Tesis y disertaciones académicas
Inhibidores naturales del fentanilo
Acoplamiento molecular y análisis ADMET
Desarrollo de alternativas terapéuticas
Crisis de opioides y seguridad farmacológica
Fentanyl
Mu opioid receptor
Secondary metabolites
Molecular docking
Natural compounds.
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id UDISTRITA2_9d0580d41dc899cbb496901a7496528e
oai_identifier_str oai:repository.udistrital.edu.co:11349/41913
network_acronym_str UDISTRITA2
network_name_str RIUD: repositorio U. Distrital
repository_id_str
dc.title.none.fl_str_mv Evaluación in silico de flavonoides como potenciales inhibidores del fentanilo
dc.title.titleenglish.none.fl_str_mv In silico evaluation of flavonoids as potential fentanyl inhibitors
title Evaluación in silico de flavonoides como potenciales inhibidores del fentanilo
spellingShingle Evaluación in silico de flavonoides como potenciales inhibidores del fentanilo
Fentanilo
Receptor opioide mu
Metabolitos secundarios
Acoplamiento molecular
Compuestos naturales.
Licenciatura en Biología -- Tesis y disertaciones académicas
Inhibidores naturales del fentanilo
Acoplamiento molecular y análisis ADMET
Desarrollo de alternativas terapéuticas
Crisis de opioides y seguridad farmacológica
Fentanyl
Mu opioid receptor
Secondary metabolites
Molecular docking
Natural compounds.
title_short Evaluación in silico de flavonoides como potenciales inhibidores del fentanilo
title_full Evaluación in silico de flavonoides como potenciales inhibidores del fentanilo
title_fullStr Evaluación in silico de flavonoides como potenciales inhibidores del fentanilo
title_full_unstemmed Evaluación in silico de flavonoides como potenciales inhibidores del fentanilo
title_sort Evaluación in silico de flavonoides como potenciales inhibidores del fentanilo
dc.creator.fl_str_mv Giraldo Muñoz, Ariany Yoaly
dc.contributor.advisor.none.fl_str_mv Mahecha Jiménez, Oscar Javier
Rodríguez Lopez, Edwin Alexander
dc.contributor.author.none.fl_str_mv Giraldo Muñoz, Ariany Yoaly
dc.contributor.orcid.none.fl_str_mv Mahecha, Oscar Javier [0000-0002-8682-0020]
dc.subject.none.fl_str_mv Fentanilo
Receptor opioide mu
Metabolitos secundarios
Acoplamiento molecular
Compuestos naturales.
topic Fentanilo
Receptor opioide mu
Metabolitos secundarios
Acoplamiento molecular
Compuestos naturales.
Licenciatura en Biología -- Tesis y disertaciones académicas
Inhibidores naturales del fentanilo
Acoplamiento molecular y análisis ADMET
Desarrollo de alternativas terapéuticas
Crisis de opioides y seguridad farmacológica
Fentanyl
Mu opioid receptor
Secondary metabolites
Molecular docking
Natural compounds.
dc.subject.lemb.none.fl_str_mv Licenciatura en Biología -- Tesis y disertaciones académicas
Inhibidores naturales del fentanilo
Acoplamiento molecular y análisis ADMET
Desarrollo de alternativas terapéuticas
Crisis de opioides y seguridad farmacológica
dc.subject.keyword.none.fl_str_mv Fentanyl
Mu opioid receptor
Secondary metabolites
Molecular docking
Natural compounds.
description La creciente preocupación por el uso del fentanilo, debido a su abuso y efectos adversos, subraya la necesidad urgente de encontrar alternativas terapéuticas más seguras. El objetivo general de esta investigación evaluar la interacción de metabolitos secundarios con el receptor opioide mu (Mor) y su uso como inhibidores de fentanilo a través de un enfoque in silico. El proceso de investigación se dividió en varias etapas clave: inicialmente, se realizó un acoplamiento molecular detallado para evaluar la interacción inicial de los compuestos con el receptor. Posteriormente, se llevó a cabo un acoplamiento masivo utilizando una amplia base de datos de compuestos naturales, seguido por un análisis ADMET para evaluar la absorción, distribución, metabolismo, excreción y toxicidad de los compuestos seleccionados. Los resultados del acoplamiento mostraron consistencia con la estructura cristalina del receptor, validando la metodología empleada. Los compuestos más prometedores fueron ZINC_1297, ZINC_287, ZINC_1299, ZINC_1474, ZINC_1793, ZINC_2014, ZINC_819, ZINC_2302, ZINC_1605, ZINC_2050, ZINC_2179 y ZINC_2513, aquellos que no violaban más de tres reglas de Lipinski, asegurando su viabilidad como fármacos orales efectivos. Además, se exploró la posible relación entre los puentes de hidrógeno y la permeabilidad de la barrera hematoencefálica, sugiriendo que estas interacciones pueden facilitar el paso de los compuestos al cerebro. En conclusión, esta investigación no solo avanza en la identificación de posibles inhibidores naturales del fentanilo, sino que también establece un marco metodológico robusto para futuras exploraciones de compuestos naturales en el tratamiento de adicciones y manejo del dolor, contribuyendo significativamente a la mitigación de la crisis de los opioides y al desarrollo de terapias más seguras y efectivas.
publishDate 2024
dc.date.accessioned.none.fl_str_mv 2024-10-22T20:52:44Z
dc.date.available.none.fl_str_mv 2024-10-22T20:52:44Z
dc.date.created.none.fl_str_mv 2024-08-05
dc.type.none.fl_str_mv bachelorThesis
dc.type.degree.none.fl_str_mv Investigación-Innovación
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/bachelorThesis
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_7a1f
format http://purl.org/coar/resource_type/c_7a1f
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/11349/41913
url http://hdl.handle.net/11349/41913
dc.language.iso.none.fl_str_mv spa
language spa
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spelling Mahecha Jiménez, Oscar JavierRodríguez Lopez, Edwin AlexanderGiraldo Muñoz, Ariany YoalyMahecha, Oscar Javier [0000-0002-8682-0020]2024-10-22T20:52:44Z2024-10-22T20:52:44Z2024-08-05http://hdl.handle.net/11349/41913La creciente preocupación por el uso del fentanilo, debido a su abuso y efectos adversos, subraya la necesidad urgente de encontrar alternativas terapéuticas más seguras. El objetivo general de esta investigación evaluar la interacción de metabolitos secundarios con el receptor opioide mu (Mor) y su uso como inhibidores de fentanilo a través de un enfoque in silico. El proceso de investigación se dividió en varias etapas clave: inicialmente, se realizó un acoplamiento molecular detallado para evaluar la interacción inicial de los compuestos con el receptor. Posteriormente, se llevó a cabo un acoplamiento masivo utilizando una amplia base de datos de compuestos naturales, seguido por un análisis ADMET para evaluar la absorción, distribución, metabolismo, excreción y toxicidad de los compuestos seleccionados. Los resultados del acoplamiento mostraron consistencia con la estructura cristalina del receptor, validando la metodología empleada. Los compuestos más prometedores fueron ZINC_1297, ZINC_287, ZINC_1299, ZINC_1474, ZINC_1793, ZINC_2014, ZINC_819, ZINC_2302, ZINC_1605, ZINC_2050, ZINC_2179 y ZINC_2513, aquellos que no violaban más de tres reglas de Lipinski, asegurando su viabilidad como fármacos orales efectivos. Además, se exploró la posible relación entre los puentes de hidrógeno y la permeabilidad de la barrera hematoencefálica, sugiriendo que estas interacciones pueden facilitar el paso de los compuestos al cerebro. En conclusión, esta investigación no solo avanza en la identificación de posibles inhibidores naturales del fentanilo, sino que también establece un marco metodológico robusto para futuras exploraciones de compuestos naturales en el tratamiento de adicciones y manejo del dolor, contribuyendo significativamente a la mitigación de la crisis de los opioides y al desarrollo de terapias más seguras y efectivas.The growing concern over the use of fentanyl, due to its abuse and adverse effects, underscores the urgent need to find safer therapeutic alternatives. The general objective of this research is to evaluate the interaction of secondary metabolites with the mu opioid receptor (MOR) and their use as fentanyl inhibitors through an in silico approach. The research process was divided into several key stages: initially, detailed molecular docking was performed to evaluate the initial interaction of the compounds with the receptor. Subsequently, massive docking was carried out using a broad database of natural compounds, followed by an ADMET analysis to evaluate the absorption, distribution, metabolism, excretion, and toxicity of the selected compounds. The docking results showed consistency with the receptor's crystal structure, validating the methodology used. The most promising compounds were ZINC_1297, ZINC_287, ZINC_1299, ZINC_1474, ZINC_1793, ZINC_2014, ZINC_819, ZINC_2302, ZINC_1605, ZINC_2050, ZINC_2179, and ZINC_2513, those that did not violate more than three of Lipinski's rules, ensuring their viability as effective oral drugs. Additionally, the possible relationship between hydrogen bonds and the permeability of the blood-brain barrier was explored, suggesting that these interactions may facilitate the passage of the compounds into the brain. In conclusion, this research not only advances the identification of potential natural inhibitors of fentanyl but also establishes a robust methodological framework for future explorations of natural compounds in addiction treatment and pain management, significantly contributing to mitigating the opioid crisis and developing safer and more effective therapies.pdfspaUniversidad Distrital Francisco José de CaldasFentaniloReceptor opioide muMetabolitos secundariosAcoplamiento molecularCompuestos naturales.Licenciatura en Biología -- Tesis y disertaciones académicasInhibidores naturales del fentaniloAcoplamiento molecular y análisis ADMETDesarrollo de alternativas terapéuticasCrisis de opioides y seguridad farmacológicaFentanylMu opioid receptorSecondary metabolitesMolecular dockingNatural compounds.Evaluación in silico de flavonoides como potenciales inhibidores del fentaniloIn silico evaluation of flavonoids as potential fentanyl inhibitorsbachelorThesisInvestigación-Innovacióninfo:eu-repo/semantics/bachelorThesishttp://purl.org/coar/resource_type/c_7a1fAbierto (Texto Completo)http://purl.org/coar/access_right/c_abf21. 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