Diseño in silico, síntesis y efecto en la actividad Ca2+ -ATPasa de CtpF de los compuestos derivados del núcleo pirrolo[1,2- a]quinoxalinas con potencial antimicobacteriano
ilustraciones, graficas, tablas
- Autores:
-
Rodriguez Afanador, Michael Daniela
- Tipo de recurso:
- Fecha de publicación:
- 2021
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/81534
- Palabra clave:
- 570 - Biología::572 - Bioquímica
Mycobacterium tuberculosis
Pyrrolo[1,2-a]quinoxalines
Deep Eutectic Solvents
Mycobacterium tuberculosis
P-type ATPase
Docking
Pirrolo[1,2-a]quinoxalinas
CtpF
Solventes Eutécticos Profundos
Mycobacterium tuberculosis
ATPasa tipo P
Acoplamiento molecular
- Rights
- openAccess
- License
- Atribución-NoComercial 4.0 Internacional
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| dc.title.spa.fl_str_mv |
Diseño in silico, síntesis y efecto en la actividad Ca2+ -ATPasa de CtpF de los compuestos derivados del núcleo pirrolo[1,2- a]quinoxalinas con potencial antimicobacteriano |
| dc.title.translated.eng.fl_str_mv |
In silico design, synthesis and effect on Ca2+ -ATPase activity of CtpF of pyrrolo[1,2- a]quinoxaline core-derived compounds with antimycobacterial potential |
| title |
Diseño in silico, síntesis y efecto en la actividad Ca2+ -ATPasa de CtpF de los compuestos derivados del núcleo pirrolo[1,2- a]quinoxalinas con potencial antimicobacteriano |
| spellingShingle |
Diseño in silico, síntesis y efecto en la actividad Ca2+ -ATPasa de CtpF de los compuestos derivados del núcleo pirrolo[1,2- a]quinoxalinas con potencial antimicobacteriano 570 - Biología::572 - Bioquímica Mycobacterium tuberculosis Pyrrolo[1,2-a]quinoxalines Deep Eutectic Solvents Mycobacterium tuberculosis P-type ATPase Docking Pirrolo[1,2-a]quinoxalinas CtpF Solventes Eutécticos Profundos Mycobacterium tuberculosis ATPasa tipo P Acoplamiento molecular |
| title_short |
Diseño in silico, síntesis y efecto en la actividad Ca2+ -ATPasa de CtpF de los compuestos derivados del núcleo pirrolo[1,2- a]quinoxalinas con potencial antimicobacteriano |
| title_full |
Diseño in silico, síntesis y efecto en la actividad Ca2+ -ATPasa de CtpF de los compuestos derivados del núcleo pirrolo[1,2- a]quinoxalinas con potencial antimicobacteriano |
| title_fullStr |
Diseño in silico, síntesis y efecto en la actividad Ca2+ -ATPasa de CtpF de los compuestos derivados del núcleo pirrolo[1,2- a]quinoxalinas con potencial antimicobacteriano |
| title_full_unstemmed |
Diseño in silico, síntesis y efecto en la actividad Ca2+ -ATPasa de CtpF de los compuestos derivados del núcleo pirrolo[1,2- a]quinoxalinas con potencial antimicobacteriano |
| title_sort |
Diseño in silico, síntesis y efecto en la actividad Ca2+ -ATPasa de CtpF de los compuestos derivados del núcleo pirrolo[1,2- a]quinoxalinas con potencial antimicobacteriano |
| dc.creator.fl_str_mv |
Rodriguez Afanador, Michael Daniela |
| dc.contributor.advisor.none.fl_str_mv |
Salazar Pulido, Luz Mary Ochoa Puentes, Cristian |
| dc.contributor.author.none.fl_str_mv |
Rodriguez Afanador, Michael Daniela |
| dc.contributor.researchgroup.spa.fl_str_mv |
Bioquímica y Biología Molecular de las Micobacterias Síntesis Orgánica Sostenible |
| dc.subject.ddc.spa.fl_str_mv |
570 - Biología::572 - Bioquímica |
| topic |
570 - Biología::572 - Bioquímica Mycobacterium tuberculosis Pyrrolo[1,2-a]quinoxalines Deep Eutectic Solvents Mycobacterium tuberculosis P-type ATPase Docking Pirrolo[1,2-a]quinoxalinas CtpF Solventes Eutécticos Profundos Mycobacterium tuberculosis ATPasa tipo P Acoplamiento molecular |
| dc.subject.other.none.fl_str_mv |
Mycobacterium tuberculosis |
| dc.subject.proposal.eng.fl_str_mv |
Pyrrolo[1,2-a]quinoxalines Deep Eutectic Solvents Mycobacterium tuberculosis P-type ATPase Docking Pirrolo[1,2-a]quinoxalinas |
| dc.subject.proposal.none.fl_str_mv |
CtpF |
| dc.subject.proposal.spa.fl_str_mv |
Solventes Eutécticos Profundos Mycobacterium tuberculosis ATPasa tipo P Acoplamiento molecular |
| description |
ilustraciones, graficas, tablas |
| publishDate |
2021 |
| dc.date.issued.none.fl_str_mv |
2021 |
| dc.date.accessioned.none.fl_str_mv |
2022-06-08T17:11:08Z |
| dc.date.available.none.fl_str_mv |
2022-06-08T17:11:08Z |
| dc.type.spa.fl_str_mv |
Trabajo de grado - Maestría |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/masterThesis |
| dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
| dc.type.content.spa.fl_str_mv |
Text |
| dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/TM |
| status_str |
acceptedVersion |
| dc.identifier.uri.none.fl_str_mv |
https://repositorio.unal.edu.co/handle/unal/81534 |
| dc.identifier.instname.spa.fl_str_mv |
Universidad Nacional de Colombia |
| dc.identifier.reponame.spa.fl_str_mv |
Repositorio Institucional Universidad Nacional de Colombia |
| dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.unal.edu.co/ |
| url |
https://repositorio.unal.edu.co/handle/unal/81534 https://repositorio.unal.edu.co/ |
| identifier_str_mv |
Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia |
| dc.language.iso.spa.fl_str_mv |
spa |
| language |
spa |
| dc.relation.references.spa.fl_str_mv |
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Atribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Salazar Pulido, Luz Maryada99096b2301478657e273ff0ee9557Ochoa Puentes, Cristian42e14d381f1b918cc0c85c77a0ec35c2Rodriguez Afanador, Michael Danielad874fd9e661a9ecb7f4e0fcc03532a67Bioquímica y Biología Molecular de las MicobacteriasSíntesis Orgánica Sostenible2022-06-08T17:11:08Z2022-06-08T17:11:08Z2021https://repositorio.unal.edu.co/handle/unal/81534Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, graficas, tablasLa Ca2+-ATPasa tipo P de CtpF de Mycobacterium tuberculosis (Mtb), es un transportador de membrana fundamental en la homeóstasis iónica y la viabilidad celular de la micobacteria; posee un sitio de unión cuya interacción con compuestos inhiben la función enzimática y la actividad micobacteriana. Teniendo en cuenta lo anterior, se postularon y estudiaron mediante estrategias in silico, compuestos con el núcleo pirrolo[1,2- a]quinoxalínico sustituido en la posición C-4 como posibles inhibidores de CtpF, ya que han mostrado en estudios anteriores un amplio perfil farmacológico, contra bacterias, virus, y con actividad antitumoral, sin embargo, su potencial antituberculoso no ha sido explorado. Consecuentemente, el objetivo de este trabajo fue diseñar, sintetizar y evaluar el efecto en la actividad Ca2+ -ATPasa de CtpF de algunos compuestos derivados del núcleo pirrolo[1,2-a]quinoxalínico con potencial antimicobacteriano. Se Identificaron los compuestos 4-(3,4-metilenedioxifenil)pirrolo[1,2-a]quinoxalina 4b y 4-(2-clorofenil)pirrolo[1,2-a]quinoxalina 4c como posibles inhibidores de CtpF por medio de un cribado virtual y acoplamiento molecular. La síntesis de ambas moléculas se realizó con el uso de Solventes de punto eutéctico bajo (DES) como disolventes y catalizadores, obteniendo tiempos de reacción cortos, alta pureza en los productos y procesos amigables con el ambiente, lo cual es una mejora en la síntesis de estos compuestos. Se estudió la inhibición de ambas moléculas sobre la actividad Ca2+ -ATPasa de CtpF, se obtuvo un 30.51% para 4c y 18.17% para 4b. El compuesto 4b presentó una Concentración Mínima Inhibitoria (CMI) interesante de 25 µg/mL, lo cual lo convierte en un candidato promisorio como posible antituberculoso. Ninguna de las moléculas presentó toxicidad sobre células eucariotas; por lo tanto, su optimización puede contribuir al desarrollo de nuevos compuestos antimicobacterianos. (Texto tomado de la fuente)The P-type Ca2+-ATPase of CtpF from Mycobacterium tuberculosis (Mtb), a membrane transporter essential for ionic homeostasis and cell viability of mycobacteria, possesses a binding site whose interaction with compounds inhibits enzymatic function and mycobacterial activity. Considering the above, compounds with the pyrrolo[1,2- a]quinoxalinic core substituted at the C-4 position were postulated and studied by in silico strategies as possible CtpF inhibitors, since they have shown in previous studies a broad pharmacological profile, against bacteria, viruses, and with antitumor activity, however, their antituberculosis potential has not been explored. Consequently, the aim of this work was to design, synthesize and evaluate the effect on the Ca2+-ATPase activity of CtpF of some compounds derived from the pyrrolo[1,2- a]quinoxaline cores with antimycobacterial potential. Compounds 4-(3,4- methylenedioxyphenyl)pyrrolo[1,2-a]quinoxalin 4b and 4-(2-chlorophenyl)pyrrolo[1,2- a]quinoxalin 4c were identified as potential CtpF inhibitors by virtual screening and molecular docking. The synthesis of both molecules was performed with the use of Low Eutectic Point Solvents (DES) as solvents and catalysts, obtaining short reaction times, high purity in the products and environmentally friendly processes, which is an improvement in the synthesis of these compounds. The inhibition of both molecules on the Ca2+ -ATPase activity of CtpF was studied, 30.51% was obtained for 4c and 18.17% for 4b. Compound 4b presented an interesting Minimum Inhibitory Concentration (MIC) of 25 µg/mL, which makes it a promising candidate as a possible antituberculous. None of the molecules showed toxicity on eukaryotic cells; therefore, their optimization may contribute to the development of new antimycobacterial compounds.MaestríaMagíster en Bioquímicaxvi, 78 paginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - BioquímicaDepartamento de QuímicaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá570 - Biología::572 - BioquímicaMycobacterium tuberculosisPyrrolo[1,2-a]quinoxalinesDeep Eutectic SolventsMycobacterium tuberculosisP-type ATPaseDockingPirrolo[1,2-a]quinoxalinasCtpFSolventes Eutécticos ProfundosMycobacterium tuberculosisATPasa tipo PAcoplamiento molecularDiseño in silico, síntesis y efecto en la actividad Ca2+ -ATPasa de CtpF de los compuestos derivados del núcleo pirrolo[1,2- a]quinoxalinas con potencial antimicobacterianoIn silico design, synthesis and effect on Ca2+ -ATPase activity of CtpF of pyrrolo[1,2- a]quinoxaline core-derived compounds with antimycobacterial potentialTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMAbbott, A. 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Drug Discovery, 12(5), 388–404. https://doi.org/10.1038/nrd4001EstudiantesORIGINALTesis de maestria Michael Daniela Rodriguez Afanador .pdfTesis de maestria Michael Daniela Rodriguez Afanador .pdfTesis de Maestría en Ciencias - Bioquímicaapplication/pdf1981150https://repositorio.unal.edu.co/bitstream/unal/81534/3/Tesis%20de%20maestria%20Michael%20Daniela%20Rodriguez%20Afanador%20.pdfdd7bce9f0f972d1e9de534c072c3ce35MD53LICENSElicense.txtlicense.txttext/plain; charset=utf-84074https://repositorio.unal.edu.co/bitstream/unal/81534/4/license.txt8153f7789df02f0a4c9e079953658ab2MD54THUMBNAILTesis de maestria Michael Daniela Rodriguez Afanador .pdf.jpgTesis de maestria Michael Daniela Rodriguez Afanador .pdf.jpgGenerated Thumbnailimage/jpeg4996https://repositorio.unal.edu.co/bitstream/unal/81534/5/Tesis%20de%20maestria%20Michael%20Daniela%20Rodriguez%20Afanador%20.pdf.jpgee5af47ae071adbce98976ad01dce0b2MD55unal/81534oai:repositorio.unal.edu.co:unal/815342023-08-04 23:04:55.715Repositorio 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