Diseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosas
| dc.contributor.advisor | Orozco Lopez, Fabian | |
| dc.contributor.author | Becerra Rivas, Christian Alonso | |
| dc.contributor.cvlac | BECERRA RIVAS, CHRISTIAN ALONSO [0001535835] | spa |
| dc.contributor.googlescholar | Christian Alonso Becerra Rivas [AJsN-F7-D4NJlHWfvCzFFoYK3QhTUbFz5pzpo46E8Bsiin981m6tOiF4UK2jLdZXDlh_SOl32nxOMRzvYaQkQpr3QZc9GaRN6A] | spa |
| dc.contributor.orcid | Christian Becerra [0000000296623813] | spa |
| dc.contributor.researchgate | Christian Alonso Becerra [Christian-Becerra] | spa |
| dc.contributor.researchgroup | Grupo de Estudios en Síntesis y Aplicaciones de Compuestos Heterocíclicos (Gesach) | spa |
| dc.date.accessioned | 2023-07-28T14:19:03Z | |
| dc.date.available | 2023-07-28T14:19:03Z | |
| dc.date.issued | 2023 | |
| dc.description | ilustraciones, diagramas | spa |
| dc.description.abstract | Los canales iónicos han despertado recientemente el interés de estudio desde la farmacología dada su potencial aplicación como dianas terapéuticas en el tratamiento de diversas patologías. En esta medida se planteó una biblioteca de compuestos de núcleo heterocíclico pirazólico, tiazolidinónico, tiazepínico y pirimidínico que pudieran interactuar con dianas moleculares de esta familia de proteínas; resultando de especial interés para este trabajo el receptor GABAA y el canal de sodio dependiente de voltaje NaV1.7. Dicha biblioteca se sometió a un proceso de cribado mediante docking molecular usando 3 programas (AutoDock4, AutoDock-VINA y DOCK6), determinación in silico de los descriptores moleculares de biodisponibilidad de Lipinski (ADME) y predicción de las propiedades toxicológicas, seleccionando los prototipos más promisorios y llevándolos a la fase de síntesis donde se estudiaron también las condiciones óptimas, así como sutilezas estructurales y de reactividad orientadas al mejoramiento de los procesos químicos que permitieron obtener con buenos rendimientos, 4 series de compuestos con un alto perfil promisorio en modulación de los canales iónicos diana para el tratamiento de enfermedades derivadas de una desregulación autonómica de las señales nerviosas. Además del nuevo conocimiento obtenido sobre los aspectos estructurales, cinéticos y termodinámicos pertinentes para la síntesis de las moléculas objetivo de interés para este estudio. | spa |
| dc.description.abstract | Ion channels have recently aroused study interest from pharmacology, given their potential usage as therapeutic targets in the treatment of diverse pathologies. To this purpose, a library of compounds with heterocyclic nucleus such as pyrazole, thiazolidine, thiazepine and pyrimidine was proposed, so that they could interact with molecular targets of this family of proteins; resulting especially interesting for the purpose of this work, GABA-A receptor and voltage gated sodium channel NaV1.7. Mentioned library was subjected to a screening process by molecular docking using three programs (AutoDock4, AutoDock-VINA, and DOCK6), in silico calculus of Lipinski bioavailability descriptors (ADME) and prediction of toxicological properties, selecting the most promising prototypes and taking them to synthesis phase, where optimal conditions as well as structural and reactivity subtleties were studied, aiming for the improvement of the chemical processes that allowed to obtain with good yields, four series of compounds with high promising profile in modulation of the target ion channels for the treatment of diseases related from autonomic deregulation of nerve signals. Besides of new knowledge acquired about the structural, kinetic and thermodynamic aspects related with the synthesis of target molecules interesting for the purposes of this work. | eng |
| dc.description.degreelevel | Doctorado | spa |
| dc.description.degreename | Doctor en Ciencias - Química | spa |
| dc.description.researcharea | Síntesis Química | spa |
| dc.description.sponsorship | Ministerio de Ciencia Tecnología e Innovación (Minciencias) | spa |
| dc.format.extent | xxviii, 369 | spa |
| dc.format.mimetype | application/pdf | spa |
| dc.identifier.instname | Universidad Nacional de Colombia | spa |
| dc.identifier.reponame | Repositorio Institucional Universidad Nacional de Colombia | spa |
| dc.identifier.repourl | https://repositorio.unal.edu.co/ | spa |
| dc.identifier.uri | https://repositorio.unal.edu.co/handle/unal/84352 | |
| dc.language.iso | spa | spa |
| dc.publisher | Universidad Nacional de Colombia | spa |
| dc.publisher.branch | Universidad Nacional de Colombia - Sede Bogotá | spa |
| dc.publisher.faculty | Facultad de Ciencias | spa |
| dc.publisher.place | Bogotá, Colombia | spa |
| dc.publisher.program | Bogotá - Ciencias - Doctorado en Ciencias - Química | spa |
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| dc.rights.accessrights | info:eu-repo/semantics/openAccess | spa |
| dc.rights.license | Atribución-NoComercial 4.0 Internacional | spa |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | spa |
| dc.subject.ddc | 540 - Química y ciencias afines::547 - Química orgánica | spa |
| dc.subject.proposal | Pirazoles | spa |
| dc.subject.proposal | Pirimidinas | spa |
| dc.subject.proposal | Tiazolidin-4-onas | spa |
| dc.subject.proposal | GABA-A | spa |
| dc.subject.proposal | Canal de sodio | spa |
| dc.subject.proposal | Síntesis orgánica | spa |
| dc.subject.proposal | Pyrazoles | eng |
| dc.subject.proposal | Pyrimidines | eng |
| dc.subject.proposal | Thiazolidin-4-ones | eng |
| dc.subject.proposal | GABA-A | eng |
| dc.subject.proposal | Sodium ion channel | eng |
| dc.subject.proposal | Organic synthesis | eng |
| dc.subject.wikidata | heterocyclic compound | eng |
| dc.subject.wikidata | compuesto heterocíclico | spa |
| dc.title | Diseño racional y síntesis de derivados heterocíclicos azufrados y nitrogenados con potencial actividad farmacológica sobre canales iónicos reguladores de las señales nerviosas | spa |
| dc.title.translated | Rational design and synthesis of sulfur and nitrogen heterocycles with potential pharmacological activity on ion channels as regulators of nervous signals | eng |
| dc.type | Trabajo de grado - Doctorado | spa |
| dc.type.coar | http://purl.org/coar/resource_type/c_db06 | spa |
| dc.type.coarversion | http://purl.org/coar/version/c_ab4af688f83e57aa | spa |
| dc.type.content | Text | spa |
| dc.type.driver | info:eu-repo/semantics/doctoralThesis | spa |
| dc.type.redcol | http://purl.org/redcol/resource_type/TD | spa |
| dc.type.version | info:eu-repo/semantics/acceptedVersion | spa |
| dcterms.audience.professionaldevelopment | Estudiantes | spa |
| dcterms.audience.professionaldevelopment | Investigadores | spa |
| dcterms.audience.professionaldevelopment | Maestros | spa |
| dcterms.audience.professionaldevelopment | Medios de comunicación | spa |
| dcterms.audience.professionaldevelopment | Proveedores de ayuda financiera para estudiantes | spa |
| oaire.accessrights | http://purl.org/coar/access_right/c_abf2 | spa |
| oaire.awardtitle | Síntesis multicomponente, cribado virtual y evaluación de la actividad tranquilizante de nuevos compuestos tiacepínicos, tiazolidínicos y quinolínicos | spa |
| oaire.fundername | Ministerio de Ciencia Tecnología e Innovación (Minciencias) | spa |
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