Dendrímeros péptido-resorcinareno: (i) obtención mediante reacción de cicloadición azida/alquino y (ii) evaluación de su potencial antibacteriano

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dc.contributor.advisorMaldona Villamil, Mauricio
dc.contributor.advisorRivera Monroy, Zuly Jenny
dc.contributor.authorPineda Castañeda, Héctor Manuel
dc.contributor.cvlachttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000073189spa
dc.contributor.googlescholarhttps://scholar.google.com/citations?user=Wu60Xw0AAAAJ&hl=es&authuser=3spa
dc.contributor.orcid0000-0002-9081-0546spa
dc.contributor.researchgatehttps://www.researchgate.net/profile/Hector-Pineda-Castanedaspa
dc.contributor.researchgroupSíntesis y Aplicación de Moléculas Peptídicasspa
dc.contributor.researchgroupAplicaciones Analíticas de Compuestos Orgánicos (Aaco)spa
dc.contributor.scopushttps://www.scopus.com/authid/detail.uri?authorId=57208139842spa
dc.date.accessioned2024-02-07T13:53:46Z
dc.date.available2024-02-07T13:53:46Z
dc.date.issued2023
dc.description.abstractLa resistencia a los antimicrobianos (RAM) es una de las diez principales amenazas para la salud pública reportadas por la Organización Mundial de la Salud (OMS). Una de las causas del creciente problema de la RAM es la falta de nuevas terapias y/o agentes de tratamiento; en consecuencia, muchas enfermedades infecciosas podrían volverse incontrolables. La necesidad de descubrir nuevos agentes antimicrobianos, que sean alternativos a los existentes, y que permitan mitigar este problema, se ha incrementado debido a la rápida y global expansión de la RAM. En este contexto, se han propuesto como alternativas para combatir la RAM tanto los péptidos antimicrobianos (PAMs) como los dendrímeros que presentan múltiples copias de compuestos antibacterianos en su estructura. Los dendrímeros han exhibido propiedades antifúngicas y antibacterianas y también se han utilizado en terapias antiinflamatorias, antineoplásicas y cardiovasculares y son útiles en sistemas de administración de fármacos y genes. En este trabajo se propuso obtener dendrímeros que presenten cuatro copias de secuencias de PAMs. Específicamente, (i) se exploró la síntesis, purificación y caracterización de dendrímeros de péptido-resorcinareno derivados de las secuencias LfcinB (20-25): RRWQWR y BF (32-35): RLLR, y (ii) la actividad antimicrobiana y citotóxica de estos dendrímeros. Se establecieron las rutas de síntesis que permitieron obtener: a) alquino-resorcinarenos y b) péptidos funcionalizados con el grupo azida; los cuales se usaron para generar c) dendrímeros de péptido-resorcinareno mediante química click de cicloadición de azida-alquino CuAAC. Finalmente, se evaluó la actividad antimicrobiana y citotóxica de los dendrímeros obtenidos frente a cepas de referencia y aislados clínicos. Estos resultados permitieron la identificación de moléculas antimicrobianas prometedoras que pueden conducir a avances en el desarrollo de nuevos agentes terapéuticos. (Texto tomado de la fuente)spa
dc.description.abstractAntimicrobial resistance (AMR) is one of the top ten threats to public health reported by the World Health Organization (WHO). One of the causes of the growing AMR problem is the lack of new therapies and/or treatment agents; consequently, many infectious diseases could become uncontrollable. The need to discover new antimicrobial agents, which are alternatives to the existing ones, and which allow mitigating this problem, has increased due to the rapid and global expansion of AMR. In this context, both antimicrobial peptides (AMPs) and dendrimers that present multiple copies of antibacterial compounds in their structure have been proposed as alternatives to combat AMR. Dendrimers have exhibited antifungal and antibacterial properties and have also been used in anti-inflammatory, antineoplastic and cardiovascular therapies and are useful in drug and gene delivery systems. In this work, it was proposed to obtain dendrimers that present four copies of AMPs sequences. Specifically, (i) the synthesis, purification, and characterization of peptide-resorcinarene dendrimers derived from the sequences LfcinB (20-25): RRWQWR and BF (32-35): RLLR, and (ii) the antimicrobial and cytotoxic activity were explored. of these dendrimers. The synthesis routes that allowed obtaining: a) alkyne-resorcinarenes and b) peptides functionalized with the azide group were established, which were used to generate c) peptide-resorcinarene dendrimers by azide-alkyne cycloaddition (CuAAC) click chemistry. Finally, the antimicrobial and cytotoxic activity of the dendrimers obtained was evaluated against reference strains and clinical isolates. These results allowed the identification of promising antimicrobial molecules that may lead to breakthroughs in the development of new therapeutic agents.eng
dc.description.degreelevelDoctoradospa
dc.description.degreenameDoctor en Ciencias - Químicaspa
dc.format.extent269 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/85642
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 - Doctorado en Ciencias - Químicaspa
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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.ddc540 - Química y ciencias afinesspa
dc.subject.decsProgramas de Optimización del Uso de los Antimicrobianosspa
dc.subject.decsAntimicrobial Stewardshipeng
dc.subject.decsAntiinfecciososspa
dc.subject.decsAnti-Infective Agentseng
dc.subject.proposalDendrimerosspa
dc.subject.proposalPéptidospa
dc.subject.proposalResorcinarenospa
dc.subject.proposalPéptidos Antimicrobianosspa
dc.subject.proposalQuímica clickspa
dc.titleDendrímeros péptido-resorcinareno: (i) obtención mediante reacción de cicloadición azida/alquino y (ii) evaluación de su potencial antibacterianospa
dc.title.translatedPeptide-resorcinarene dendrimers: (i) obtaining by azide/alkyne cycloaddition reaction and (ii) evaluation of their antibacterial potentialeng
dc.typeTrabajo de grado - Doctoradospa
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dcterms.audience.professionaldevelopmentInvestigadoresspa
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oaire.awardtitleDiseño y obtención de nuevos agentes antibacterianos basados en dendrímeros péptido-resorcinareno: Una alternativa para combatir la resistencia bacterianaspa
oaire.fundernameMincienciasspa

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