Exploration of novel inhibitors of mycobacterium tuberculosis dihydrofolate reductase for tuberculosis treatment

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Tuberculosis is a lethal illness caused by Mycobacterium tuberculosis, considered, to date, the second global cause of death. Despite this fact, the treatment still relies on 40-year-old paradigms, and with the rise of resistant tuberculosis cases and complications due to HIV coinfection, the need f...

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Detalles Bibliográficos
Autor: Mollo Palomino, Kelly Cristina
Formato: tesis de grado
Fecha de Publicación:2024
Institución:Pontificia Universidad Católica del Perú
Repositorio:PUCP-Tesis
Lenguaje:español
OAI Identifier:oai:tesis.pucp.edu.pe:20.500.12404/27723
Enlace del recurso:http://hdl.handle.net/20.500.12404/27723
Nivel de acceso:acceso abierto
Materia:Tuberculosis--Tratamiento
Moléculas
Bioquímica
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dc.title.es_ES.fl_str_mv Exploration of novel inhibitors of mycobacterium tuberculosis dihydrofolate reductase for tuberculosis treatment
title Exploration of novel inhibitors of mycobacterium tuberculosis dihydrofolate reductase for tuberculosis treatment
spellingShingle Exploration of novel inhibitors of mycobacterium tuberculosis dihydrofolate reductase for tuberculosis treatment
Mollo Palomino, Kelly Cristina
Tuberculosis--Tratamiento
Moléculas
Bioquímica
https://purl.org/pe-repo/ocde/ford#1.04.00
title_short Exploration of novel inhibitors of mycobacterium tuberculosis dihydrofolate reductase for tuberculosis treatment
title_full Exploration of novel inhibitors of mycobacterium tuberculosis dihydrofolate reductase for tuberculosis treatment
title_fullStr Exploration of novel inhibitors of mycobacterium tuberculosis dihydrofolate reductase for tuberculosis treatment
title_full_unstemmed Exploration of novel inhibitors of mycobacterium tuberculosis dihydrofolate reductase for tuberculosis treatment
title_sort Exploration of novel inhibitors of mycobacterium tuberculosis dihydrofolate reductase for tuberculosis treatment
author Mollo Palomino, Kelly Cristina
author_facet Mollo Palomino, Kelly Cristina
author_role author
dc.contributor.advisor.fl_str_mv Maruenda Castillo, Helena
dc.contributor.author.fl_str_mv Mollo Palomino, Kelly Cristina
dc.subject.es_ES.fl_str_mv Tuberculosis--Tratamiento
Moléculas
Bioquímica
topic Tuberculosis--Tratamiento
Moléculas
Bioquímica
https://purl.org/pe-repo/ocde/ford#1.04.00
dc.subject.ocde.es_ES.fl_str_mv https://purl.org/pe-repo/ocde/ford#1.04.00
description Tuberculosis is a lethal illness caused by Mycobacterium tuberculosis, considered, to date, the second global cause of death. Despite this fact, the treatment still relies on 40-year-old paradigms, and with the rise of resistant tuberculosis cases and complications due to HIV coinfection, the need for new anti-tuberculosis agents becomes urgent. An attractive target to consider for designing new drugs to fight tuberculosis is the enzyme Mycobacterium tuberculosis dihydrofolate reductase (MtbDHFR), key macromolecule in the folate pathway whose inhibition would arrest DNA synthesis in the bacteria and lead to its death. This thesis explores the molecular scaffolds reported during the last decade as virtual and in vitro inhibitors of MtbDHFR that could be used as leads for further development. Also, it covers the state of the art of MtbDHFR, in comparison with its human counterpart and the strategies used in the discovery of the selected inhibitors.
publishDate 2024
dc.date.accessioned.none.fl_str_mv 2024-05-02T20:22:59Z
dc.date.available.none.fl_str_mv 2024-05-02T20:22:59Z
dc.date.created.none.fl_str_mv 2024
dc.date.issued.fl_str_mv 2024-05-02
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dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/20.500.12404/27723
url http://hdl.handle.net/20.500.12404/27723
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dc.publisher.es_ES.fl_str_mv Pontificia Universidad Católica del Perú
dc.publisher.country.es_ES.fl_str_mv PE
dc.source.none.fl_str_mv reponame:PUCP-Tesis
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spelling Maruenda Castillo, HelenaMollo Palomino, Kelly Cristina2024-05-02T20:22:59Z2024-05-02T20:22:59Z20242024-05-02http://hdl.handle.net/20.500.12404/27723Tuberculosis is a lethal illness caused by Mycobacterium tuberculosis, considered, to date, the second global cause of death. Despite this fact, the treatment still relies on 40-year-old paradigms, and with the rise of resistant tuberculosis cases and complications due to HIV coinfection, the need for new anti-tuberculosis agents becomes urgent. An attractive target to consider for designing new drugs to fight tuberculosis is the enzyme Mycobacterium tuberculosis dihydrofolate reductase (MtbDHFR), key macromolecule in the folate pathway whose inhibition would arrest DNA synthesis in the bacteria and lead to its death. This thesis explores the molecular scaffolds reported during the last decade as virtual and in vitro inhibitors of MtbDHFR that could be used as leads for further development. Also, it covers the state of the art of MtbDHFR, in comparison with its human counterpart and the strategies used in the discovery of the selected inhibitors.La tuberculosis, enfermedad letal causada por la bacteria Mycobacterium tuberculosis, es considerada a la fecha la segunda principal causa de muerte a nivel global. A pesar de ello, el tratamiento contra la tuberculosis todavía se basa en paradigmas propuestos hace más de 40 años, y, con el incremento en los casos de tuberculosis resistente a fármacos y las complicaciones debido a la infección simultánea con VIH, la necesidad de identificar nuevos agentes contra la tuberculosis es una realidad. Un blanco terapéutico a considerar en esta lucha es la enzima dihidrofolato reductasa de Mycobacterium tuberculosis (MtbDHFR), una macromolécula clave en el ciclo del folato cuya inhibición detendría la síntesis del ADN en la bacteria, llevándola a su muerte. Esta tesis busca explorar los esqueletos moleculares de inhibidores de MtbDHFR – virtuales e in vitro – reportados en la literatura durante la última década, los cuales podrían ser empleados como moléculas líderes para un posterior desarrollo. Además, en esta tesis se cubre el estado del arte de la MtbDHFR, en comparación con su contraparte humana, y las estrategias usadas para el descubrimiento de los inhibidores aquí presentados.Trabajo de investigaciónspaPontificia Universidad Católica del PerúPEinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/2.5/pe/Tuberculosis--TratamientoMoléculasBioquímicahttps://purl.org/pe-repo/ocde/ford#1.04.00Exploration of novel inhibitors of mycobacterium tuberculosis dihydrofolate reductase for tuberculosis treatmentinfo:eu-repo/semantics/bachelorThesisreponame:PUCP-Tesisinstname:Pontificia Universidad Católica del Perúinstacron:PUCPSUNEDUBachiller en Ciencias con mención en QuímicaBachilleratoPontificia Universidad Católica del Perú. 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Exploration of novel inhibitors of mycobacterium tuberculosis dihydrofolate reductase for tuberculosis treatment
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