Diseño basado en el receptor, cribado virtual y estudios de docking molecular de nuevos inhibidores de acetilcolinesterasa humana con potencial aplicación terapéutica

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dc.contributor.advisorOrozco López, Fabianspa
dc.contributor.authorSilva Valero, Diego Alejandrospa
dc.contributor.researchgroupGrupo de Estudios en Síntesis y Aplicaciones de Compuestos Heterocíclicos (Gesach)spa
dc.date.accessioned2025-04-03T20:09:46Z
dc.date.available2025-04-03T20:09:46Z
dc.date.issued2023
dc.descriptionilustraciones, diagramasspa
dc.description.abstractLa enfermedad de Alzheimer es la causa principal de demencia y preocupa por su acelerado crecimiento, proyectándose a 113 millón de afectados para el año 2050. Este trastorno impacta significativamente las capacidades cognitivas, afectando la vida social y laboral de los individuos. Los tres tratamientos actuales, limitados a tres fármacos: donepezilo, galantamina y rivastigmina; enfrentan eventos adversos y múltiples administraciones diarias, desafiando la adherencia del paciente. Este proyecto se enfocó en desarrollar inhibidores de acetilcolinesterasa mediante un enfoque in silico. Primero se identificaron las características farmacofóricas de estos inhibidores para llevar a cabo una búsqueda de moléculas que cumplieran con éstas en la base de datos ZINC 12. Las moléculas obtenidas se sometieron a un cribado virtual, donde más del 70% mostró una energía de afinidad inferior a la del donepezilo. Luego se evaluaron las propiedades farmacocinéticas de las moléculas mejor puntuadas y se seleccionaron las dos más prometedoras. A partir de estas, se propusieron siete análogos optimizados que tuvieran mayor afinidad por el receptor con características toxicológicas y farmacocinéticas favorables (Texto tomado de la fuente).spa
dc.description.abstractAlzheimer’s disease is the principal cause of dementia rising concern due to its escalating prevalence, with projections indicating 113 million affected individuals by 2050. This disease affects cognitive capacities that damage the social and work life of individuals. Nowadays there are three available pharmacological treatments (donepezil, galantamine, and rivastigmine) that carry various adverse effects and multiple doses a day which represent a challenge to the adherence to this treatment. The aim of this project is to develop acetylcholinesterase inhibitors from a in silico approach. First, the characteristics of the pharmacophore were identified to then perform a research of molecules that satisfied these characteristics in the database ZINC 12. The obtained molecules were put through a virtual screening in which more than 70% showed a smaller affinity energy than donepezil. Pharmacokinetic properties were then evaluated in the molecules with higher scores, from which the two most promising ones were selected. From these, seven optimized analogues were proposed so that they presented greater affinity for the receptor with favorable toxicological and pharmacokinetic characteristics.eng
dc.description.degreelevelPregradospa
dc.description.degreenameQuímico Farmacéuticospa
dc.format.extent76 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/87838
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Ciencias - Farmaciaspa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseReconocimiento 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/spa
dc.subject.ddc610 - Medicina y salud::615 - Farmacología y terapéuticaspa
dc.subject.ddc540 - Química y ciencias afines::547 - Química orgánicaspa
dc.subject.decsEnfermedad de Alzheimerspa
dc.subject.decsAlzheimer Diseaseeng
dc.subject.decsDemenciaspa
dc.subject.decsDementiaeng
dc.subject.decsDonepezilospa
dc.subject.decsDonepezileng
dc.subject.decsGalantaminaspa
dc.subject.decsGalantamineeng
dc.subject.decsRivastigminaspa
dc.subject.decsRivastigmineeng
dc.subject.decsQuímica Farmacéuticaspa
dc.subject.decsChemistry, Pharmaceuticaleng
dc.subject.decsInhibidores de la Colinesterasaspa
dc.subject.decsCholinesterase Inhibitorseng
dc.subject.proposalEnfermedad de Alzheimerspa
dc.subject.proposalAcetilcolinesterasaspa
dc.subject.proposalDocking molecularspa
dc.subject.proposalCribado virtualspa
dc.subject.proposalFarmacóforospa
dc.subject.proposalAlzehimer’s diseaseeng
dc.subject.proposalAcetylcholinesteraseeng
dc.subject.proposalMolecular dockingeng
dc.subject.proposalVirtual screeningeng
dc.subject.proposalPharmacophoreeng
dc.titleDiseño basado en el receptor, cribado virtual y estudios de docking molecular de nuevos inhibidores de acetilcolinesterasa humana con potencial aplicación terapéuticaspa
dc.title.translatedReceptor-based drug design, virtual screening and molecular docking studies for new human acetylcholinesterase inhibitors with potential therapeutic applicationeng
dc.typeTrabajo de grado - Pregradospa
dc.type.coarhttp://purl.org/coar/resource_type/c_7a1fspa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/bachelorThesisspa
dc.type.redcolhttp://purl.org/redcol/resource_type/TPspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
dcterms.audience.professionaldevelopmentEstudiantesspa
dcterms.audience.professionaldevelopmentInvestigadoresspa
dcterms.audience.professionaldevelopmentMaestrosspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa

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