Antioxidantes y/o fotoprotectores de los líquenes del páramo de Sumapaz Thamnolia vermicularis y Cladonia cf. didyma y estudio de su posible producción biotecnológica

ilustraciones, diagramas, fotografías

Autores:
Nuñez Arango , Lissy Marcella
Tipo de recurso:
Doctoral thesis
Fecha de publicación:
2022
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/85287
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/85287
https://repositorio.unal.edu.co/
Palabra clave:
540 - Química y ciencias afines::542 - Técnicas, procedimientos, aparatos, equipos, materiales
líquenes
tecnología farmacéutica
antioxidantes
Lichens
Technology, Pharmaceutical
Antioxidants
Hongos liquenizados
Fotoprotección
Antioxidantes
Protección ADN
Citoprotección
Inmovilización celular
Lichenized fungi
Photoprotection
Antioxidants
DNA protection
Cytoprotection
Cell immobilization
Rights
openAccess
License
Atribución-NoComercial-CompartirIgual 4.0 Internacional
id UNACIONAL2_a594e786bb1892895ec2416ffc1a78fb
oai_identifier_str oai:repositorio.unal.edu.co:unal/85287
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Antioxidantes y/o fotoprotectores de los líquenes del páramo de Sumapaz Thamnolia vermicularis y Cladonia cf. didyma y estudio de su posible producción biotecnológica
dc.title.translated.eng.fl_str_mv Antioxidants and/or photoprotectors from the Sumapaz páramo lichens Thamnolia vermicularis and Cladonia cf. didyma and study of their possible biotechnological production
title Antioxidantes y/o fotoprotectores de los líquenes del páramo de Sumapaz Thamnolia vermicularis y Cladonia cf. didyma y estudio de su posible producción biotecnológica
spellingShingle Antioxidantes y/o fotoprotectores de los líquenes del páramo de Sumapaz Thamnolia vermicularis y Cladonia cf. didyma y estudio de su posible producción biotecnológica
540 - Química y ciencias afines::542 - Técnicas, procedimientos, aparatos, equipos, materiales
líquenes
tecnología farmacéutica
antioxidantes
Lichens
Technology, Pharmaceutical
Antioxidants
Hongos liquenizados
Fotoprotección
Antioxidantes
Protección ADN
Citoprotección
Inmovilización celular
Lichenized fungi
Photoprotection
Antioxidants
DNA protection
Cytoprotection
Cell immobilization
title_short Antioxidantes y/o fotoprotectores de los líquenes del páramo de Sumapaz Thamnolia vermicularis y Cladonia cf. didyma y estudio de su posible producción biotecnológica
title_full Antioxidantes y/o fotoprotectores de los líquenes del páramo de Sumapaz Thamnolia vermicularis y Cladonia cf. didyma y estudio de su posible producción biotecnológica
title_fullStr Antioxidantes y/o fotoprotectores de los líquenes del páramo de Sumapaz Thamnolia vermicularis y Cladonia cf. didyma y estudio de su posible producción biotecnológica
title_full_unstemmed Antioxidantes y/o fotoprotectores de los líquenes del páramo de Sumapaz Thamnolia vermicularis y Cladonia cf. didyma y estudio de su posible producción biotecnológica
title_sort Antioxidantes y/o fotoprotectores de los líquenes del páramo de Sumapaz Thamnolia vermicularis y Cladonia cf. didyma y estudio de su posible producción biotecnológica
dc.creator.fl_str_mv Nuñez Arango , Lissy Marcella
dc.contributor.advisor.spa.fl_str_mv Valencia-Islas, Norma Angélica
Rojas Araque, José Leopoldo
dc.contributor.author.spa.fl_str_mv Nuñez Arango , Lissy Marcella
dc.contributor.researchgroup.spa.fl_str_mv Grupo de Investigación en Estudios Biológicos y Fisicoquímicos de Líquenes Colombianos
Grupo de Investigación en Química Medicinal
dc.subject.ddc.spa.fl_str_mv 540 - Química y ciencias afines::542 - Técnicas, procedimientos, aparatos, equipos, materiales
topic 540 - Química y ciencias afines::542 - Técnicas, procedimientos, aparatos, equipos, materiales
líquenes
tecnología farmacéutica
antioxidantes
Lichens
Technology, Pharmaceutical
Antioxidants
Hongos liquenizados
Fotoprotección
Antioxidantes
Protección ADN
Citoprotección
Inmovilización celular
Lichenized fungi
Photoprotection
Antioxidants
DNA protection
Cytoprotection
Cell immobilization
dc.subject.decs.spa.fl_str_mv líquenes
tecnología farmacéutica
antioxidantes
dc.subject.decs.eng.fl_str_mv Lichens
Technology, Pharmaceutical
Antioxidants
dc.subject.proposal.spa.fl_str_mv Hongos liquenizados
Fotoprotección
Antioxidantes
Protección ADN
Citoprotección
Inmovilización celular
dc.subject.proposal.eng.fl_str_mv Lichenized fungi
Photoprotection
Antioxidants
DNA protection
Cytoprotection
Cell immobilization
description ilustraciones, diagramas, fotografías
publishDate 2022
dc.date.issued.none.fl_str_mv 2022
dc.date.accessioned.none.fl_str_mv 2024-01-15T18:50:49Z
dc.date.available.none.fl_str_mv 2024-01-15T18:50:49Z
dc.type.spa.fl_str_mv Trabajo de grado - Doctorado
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/doctoralThesis
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_db06
dc.type.content.spa.fl_str_mv Text
dc.type.redcol.spa.fl_str_mv http://purl.org/redcol/resource_type/TD
format http://purl.org/coar/resource_type/c_db06
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/85287
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/85287
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.indexed.spa.fl_str_mv Bireme
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spelling Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Valencia-Islas, Norma Angélicab01fa11c56a7ba9e238e81d54c8cca67600Rojas Araque, José Leopoldob9b96afb7647fc037468d5fd509d8710600Nuñez Arango , Lissy Marcella7ecc63a15e0bb09f9dc9d374c0bc4c42600Grupo de Investigación en Estudios Biológicos y Fisicoquímicos de Líquenes ColombianosGrupo de Investigación en Química Medicinal2024-01-15T18:50:49Z2024-01-15T18:50:49Z2022https://repositorio.unal.edu.co/handle/unal/85287Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, diagramas, fotografíasLa exposición prolongada a la radiación ultravioleta (RUV) afecta principalmente a la piel, generando efectos negativos agudos y crónicos, que implican lesiones mutagénicas mediadas por el estrés oxidativo (EO), conllevando a cáncer de piel, enfermedad con un alto nivel de incidencia y mortalidad. Por lo anterior, es importante el uso de sustancias que tengan propiedades fotoprotectoras y/o antioxidantes, que por un lado sean capaces de interactuar con la RUV, evitando que llegue a la piel y, por otro, que impidan o contrarresten la formación de radicales libres. Dada las limitaciones que presenta la actual oferta de agentes protectores solares y/o antioxidantes respecto a su estabilidad, eficacia y seguridad, existe la necesidad de encontrar alternativas que cumplan con dichos requisitos, y los compuestos de origen natural son de interés para este propósito. Los líquenes del páramo de Sumapaz (ecosistema sometido a condiciones ambientales extremas de alta radiación solar), son una fuente atractiva para el desarrollo de estos agentes, ya que presentan una química única, responsable en gran medida de la supervivencia que poseen estos organismos en dicho ecosistema. Es así como en la presente investigación se sometieron a estudio dos líquenes del páramo del Sumapaz, Thamnolia vermicularis y Cladonia cf. didyma, de donde se aislaron y caracterizaron al ácido descarboxythamnólico (1) y arabitol (2) del primero, y el 5α,8α-peroxiergosteril divaricatinato (3), el ácido barbático (4), el ácido condidymico (5), y el ácido isodidymico (6) del segundo. Así mismo se realizó el estudio del potencial antioxidante in vitro de los compuestos y extractos liquénicos, evaluando su capacidad captadora de radicales libres DPPH•, poder reductor férrico, poder inhibidor de la peroxidación lipídica, protección del ADN, y de queratinocitos frente al radical hidroxilo generado in situ. Se evalúo además la capacidad fotoprotectora in vitro, tanto en el UVA como en el UVB, y se determinaron parámetros fisicoquímicos: lipofilicidad (cLogP), energía libre de Gibbs de transferencia (ΔtG), área de superficie polar topológica (TPSA), peso molecular (PM) y número de anillos aromáticos que presentan en la estructura (Ar), indicativos de la penetración dérmica de los compuestos. Finalmente, se propuso una alternativa biotecnológica de inmovilización celular en caolinita como soporte de inmovilización y acetato de sodio (0.1, 1.0 y 10 mM) como precursor biosintético para la obtención de 1 a partir de T. vermicularis. El compuesto 1 resultó ser el mejor agente dual con propiedades antioxidantes y fotoprotectoras capaz de captar radicales libres (CE50 = 0.3077 mol de compuesto / mol DPPH•), reducir iones férricos (PRF 0.782 ± 0.011 a 500 ppm), proteger a las células (% viabilidad celular (%VC) 85.34 ± 2.60 a 15 μM), y a su vez posee capacidad fotoprotectora alta tanto en el UVB (FPS 39.77 ± 0.21) como en el UVA (crit 358.0 nm ± 2.1, y UVA-r* 0.546 ± 0.051 a 200 ppm) y propiedades fisicoquímicas favorables para ser entregado al estrato córneo de la piel (cLogP, ΔtG, PM y Ar#). El compuesto 3, no fue un agente antioxidante sobresaliente en los modelos empleados, sin embargo, presentó alta capacidad fotoprotectora UVA (crit 352.5 ± 1.3 y UVA-r* 0.464 ± 0.001 a 200 ppm) y propiedades protectoras de queratinocitos (%VC 82.17 ± 1.64 a 15 μM) y del ADN (% Integridad del ADN (% I-ADN) 73.82 ± 5.44 a 100 μM) frente a daño oxidativo, además de cumplir algunas propiedades fisicoquímicas para ejercer su efecto tópico (ΔtG, TPSA y Ar#). Los compuestos 5 y 6 presentaron actividad antioxidante prometedora, captando radicales libres DPPH• (CE50 = 0.6694 y 1.700 mol de compuesto / mol DPPH•, respectivamente), reducen iones férricos (PRF 0.392 ± 0.009 y 0.546 ± 0.011, respectivamente a 500 ppm), protegen a las células (% VC 76.03 ± 2.45, y 75.92 ± 0.14, respectivamente a 15 μM) y al ADN de daño oxidativo (% I-ADN 56.59 ± 4.50, y 57.44 ± 3.48, respectivamente a 100 μM) y presentan propiedades fotoprotectoras UVB altas (FPS 39.78 ± 0.20, y 38.64 ± 0.60, respectivamente a 200 ppm), además de cumplir algunas propiedades fisicoquímicas para ejercer su efecto tópico (ΔtG, TPSA y PM). Por su parte, 4 careció de propiedades antioxidantes y fotoprotectoras sobresalientes. La inmovilización celular de T. vermicularis con flujo continuo de acetato de sodio 10 mM como precursor biosintético permitió la bioproducción de 1 con el mayor rendimiento (ca. 42 %) en comparación a las otras concentraciones evaluadas del precursor. El ácido descarboxythamnólico (1) es un agente dual antioxidante y fotoprotector prometedor para su posible desarrollo como protector solar, mientras que 3, 5 y 6 son de interés para combinarlos con otros agentes en el desarrollo de protectores solares de amplio espectro. La presente investigación representa un aporte al conocimiento químico y de actividad biológica de los líquenes del páramo de Sumapaz y contribuye a la explotación sostenible de este recurso natural. (Texto tomado de la fuente).Prolonged exposure to ultraviolet radiation (UVR) mainly affects the skin, generating acute and chronic negative effects, involving mutagenic lesions mediated by oxidative stress (OS), leading to skin cancer, a disease with a high incidence and mortality rate. Therefore, it is important to use substances with photoprotective and/or antioxidant properties, which on the one hand can interact with UVR, preventing it from reaching the skin, and on the other hand, preventing or counteracting the formation of free radicals. Given the limitations of the current supply of sunscreen and/or antioxidant agents with respect to their stability, efficacy and safety, there is a need to find alternatives that meet these requirements, and compounds of natural origin are of interest for this purpose. The lichens of the Sumapaz paramo (an ecosystem subjected to extreme environmental conditions of high solar radiation), are an attractive source for the development of these agents, since they present a unique chemistry, which is largely responsible for the survival of these organisms in this ecosystem. Thus, in the present investigation, two lichens from the Sumapaz paramo, Thamnolia vermicularis and Cladonia cf. didyma, were studied, from which decarboxythamnolic acid (1) and arabitol (2) were isolated and characterized from the first one, and 5α,8α-peroxyergosteryl divaricatinate (3), barbatic acid (4), condidymic acid (5), and isodidymic acid (6) from the second one. The in vitro antioxidant potential of the compounds and lichen extracts was also studied, evaluating their DPPH• free radical scavenging capacity, ferric reducing power, lipid peroxidation inhibiting power, DNA protection, and protection of keratinocytes against the hydroxyl radical generated in situ. The in vitro photoprotective capacity was also evaluated, both in UVA and UVB, and physicochemical parameters were determined: lipophilicity (cLogP), Gibbs free energy of transfer (ΔtG), topological polar surface area (TPSA), molecular weight (MW) and number of aromatic rings present in the structure (Ar), indicative of the dermal penetration of the compounds. Finally, a biotechnological alternative of cell immobilization on kaolinite as immobilization support and sodium acetate (0.1, 1.0 and 10 mM) as biosynthetic precursor was proposed to obtain 1 from T. vermicularis. Compound 1 proved to be the best dual agent with antioxidant and photoprotective properties capable of scavenging free radicals (EC50 = 0.3077 mol compound / mol DPPH•), reducing ferric ions (PRF 0.782 ± 0.011 at 500 ppm), protecting cells (% cell viability (%VC) 85. 34 ± 2.60 at 15 μM), while possessing high photoprotective capacity in both UVB (SPF 39.77 ± 0.21) and UVA (crit 358.0 nm ± 2.1, and UVA-r* 0.546 ± 0.051 at 200 ppm) and favorable physicochemical properties for delivery to the stratum corneum of the skin (cLogP, ΔtG, PM and Ar#). Compound 3, was not an outstanding antioxidant agent in the models employed, however, it presented high UVA photoprotective capacity (crit 352.5 ± 1.3 and UVA-r* 0.464 ± 0.001 at 200 ppm) and keratinocyte protective properties (%VC 82. 17 ± 1.64 at 15 μM) and DNA (% DNA Integrity (% I-DNA) 73.82 ± 5.44 at 100 μM) against oxidative damage, in addition to fulfilling some physicochemical properties to exert their topical effect (ΔtG, TPSA and Ar#). Compounds 5 and 6 showed promising antioxidant activity, scavenging DPPH• free radicals (EC50 = 0.6694 and 1.700 mol compound / mol DPPH•, respectively), reduce ferric ions (PRF 0.392 ± 0.009 and 0.546 ± 0.011, respectively at 500 ppm), protect cells (% VC 76.03 ± 2.45, and 75.92 ± 0. 14, respectively at 15 μM) and DNA from oxidative damage (% I-DNA 56.59 ± 4.50, and 57.44 ± 3.48, respectively at 100 μM) and exhibit high UVB photoprotective properties (SPF 39.78 ± 0.20, and 38.64 ± 0.60, respectively at 200 ppm), in addition to fulfilling some physicochemical properties to exert their topical effect (ΔtG, TPSA and PM). For its part, 4 lacked outstanding antioxidant and photoprotective properties. Cell immobilization of T. vermicularis with continuous flow of 10 mM sodium acetate as biosynthetic precursor allowed the bioproduction of 1 with the highest yield (ca. 42 %) compared to the other evaluated concentrations of the precursor. Decarboxythamnolic acid (1) is a promising dual antioxidant and photoprotective agent for possible development as a sunscreen, while 3, 5 and 6 are of interest for combination with other agents in the development of broad spectrum sunscreens. The present research represents a contribution to the chemical knowledge and biological activity of the lichens of the Sumapaz paramo and contributes to the sustainable exploitation of this natural resource.Ministerio de Ciencia Tecnología e Innovación (MinCiencias) la financiación de esta tesis a través de los siguientes mecanismos: a) Programa de Créditos Condonables a Doctores Nacionales a través de la convocatoria 757, código HERMES: 43541. b) Proyecto: “Caracterización y evaluación de dispositivos médicos a base de colágeno asociados a extractos naturales y metabolitos con aplicación farmacéutica. Código: 110180864505”. CT80740-198-2019. Ministerio de Ciencia Tecnología e Innovación (MinCiencias). Código HERMES: 42660.Universidad Nacional de Colombia el financiamiento otorgado a través del proyecto: “Bioprospección de líquenes del Páramo de Sumapaz, Colombia como fuente original de sustancias duales con actividad antioxidante y fotoprotectora para la prevención de problemas dérmicos asociados a la radiación solar”, código HERMES: 35978. Convocatoria Nacional de Proyectos para el Fortalecimiento de la Investigación, Creación e Innovación de la Universidad Nacional de Colombia 2016-2018. Modalidad Única.DoctoradoDoctor en Ciencias Farmacéuticas197 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Doctorado en Ciencias FarmacéuticasFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá540 - Química y ciencias afines::542 - Técnicas, procedimientos, aparatos, equipos, materialeslíquenestecnología farmacéuticaantioxidantesLichensTechnology, PharmaceuticalAntioxidantsHongos liquenizadosFotoprotecciónAntioxidantesProtección ADNCitoprotecciónInmovilización celularLichenized fungiPhotoprotectionAntioxidantsDNA protectionCytoprotectionCell immobilizationAntioxidantes y/o fotoprotectores de los líquenes del páramo de Sumapaz Thamnolia vermicularis y Cladonia cf. didyma y estudio de su posible producción biotecnológicaAntioxidants and/or photoprotectors from the Sumapaz páramo lichens Thamnolia vermicularis and Cladonia cf. didyma and study of their possible biotechnological productionTrabajo de grado - Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_db06Texthttp://purl.org/redcol/resource_type/TDBiremeAddor, F. 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Protocols in Lichenology: culturing, biochemistry, ecophysiology and use in biomonitoring, 3-33.Bioprospección de líquenes del Páramo de Sumapaz, Colombia como fuente original de sustancias duales con actividad antioxidante y fotoprotectora para la prevención de problemas dérmicos asociados a la radiación solar”Caracterización y evaluación de dispositivos médicos a base de colágeno asociados a extractos naturales y metabolitos con aplicación farmacéutica.Ministerio de Ciencia Tecnología e Innovación (MinCiencias).Universidad Nacional de ColombiaEstudiantesInvestigadoresMaestrosPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/85287/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL53907201.2022.pdf53907201.2022.pdfTesis de Doctorado en Ciencias Farmacéuticasapplication/pdf4778945https://repositorio.unal.edu.co/bitstream/unal/85287/2/53907201.2022.pdf47e3e975542e7231bdf93db27d980237MD52unal/85287oai:repositorio.unal.edu.co:unal/852872024-01-15 13:52:21.906Repositorio Institucional Universidad Nacional de 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