Estudio químico del extracto de la corteza de Dguetia vallicola (Annonaceae), actividad antimicrobiana y antioxidante
Duguetia es un género de plantas perteneciente a la familia Annonaceae. Comprende alrededor de 100 especies, de las cuales, 28 se reportan en regiones pantropicales de Colombia. Varios de sus miembros son reconocidos por sus propiedades antioxidantes. Duguetia vallicola, popularmente conocida como “...
- Autores:
-
Padron Calderon, Jose Raul
- Tipo de recurso:
- Trabajo de grado de pregrado
- Fecha de publicación:
- 2024
- Institución:
- Universidad de Córdoba
- Repositorio:
- Repositorio Institucional Unicórdoba
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unicordoba.edu.co:ucordoba/8645
- Acceso en línea:
- https://repositorio.unicordoba.edu.co/handle/ucordoba/8645
https://repositorio.unicordoba.edu.co/
- Palabra clave:
- Duguetia
Annonaceae
Antioxidantes
UHPLC-QTof-MS/MS
Alcaloides
Duguetia
Annonaceae
Antioxidants
UHPLC-QTof-MS/MS/MS,
Alkaloids
- Rights
- embargoedAccess
- License
- Copyright Universidad de Córdoba, 2024
id |
UCORDOBA2_f212edcbc4e488d28288836f9f099e72 |
---|---|
oai_identifier_str |
oai:repositorio.unicordoba.edu.co:ucordoba/8645 |
network_acronym_str |
UCORDOBA2 |
network_name_str |
Repositorio Institucional Unicórdoba |
repository_id_str |
|
dc.title.none.fl_str_mv |
Estudio químico del extracto de la corteza de Dguetia vallicola (Annonaceae), actividad antimicrobiana y antioxidante |
title |
Estudio químico del extracto de la corteza de Dguetia vallicola (Annonaceae), actividad antimicrobiana y antioxidante |
spellingShingle |
Estudio químico del extracto de la corteza de Dguetia vallicola (Annonaceae), actividad antimicrobiana y antioxidante Duguetia Annonaceae Antioxidantes UHPLC-QTof-MS/MS Alcaloides Duguetia Annonaceae Antioxidants UHPLC-QTof-MS/MS/MS, Alkaloids |
title_short |
Estudio químico del extracto de la corteza de Dguetia vallicola (Annonaceae), actividad antimicrobiana y antioxidante |
title_full |
Estudio químico del extracto de la corteza de Dguetia vallicola (Annonaceae), actividad antimicrobiana y antioxidante |
title_fullStr |
Estudio químico del extracto de la corteza de Dguetia vallicola (Annonaceae), actividad antimicrobiana y antioxidante |
title_full_unstemmed |
Estudio químico del extracto de la corteza de Dguetia vallicola (Annonaceae), actividad antimicrobiana y antioxidante |
title_sort |
Estudio químico del extracto de la corteza de Dguetia vallicola (Annonaceae), actividad antimicrobiana y antioxidante |
dc.creator.fl_str_mv |
Padron Calderon, Jose Raul |
dc.contributor.advisor.none.fl_str_mv |
Angulo Ortiz, Alberto Antonio |
dc.contributor.author.none.fl_str_mv |
Padron Calderon, Jose Raul |
dc.contributor.jury.none.fl_str_mv |
Valle Zapata, Hernan Alonso Marin Severiche, Fernis Jose |
dc.subject.proposal.none.fl_str_mv |
Duguetia Annonaceae Antioxidantes UHPLC-QTof-MS/MS Alcaloides |
topic |
Duguetia Annonaceae Antioxidantes UHPLC-QTof-MS/MS Alcaloides Duguetia Annonaceae Antioxidants UHPLC-QTof-MS/MS/MS, Alkaloids |
dc.subject.keywords.none.fl_str_mv |
Duguetia Annonaceae Antioxidants UHPLC-QTof-MS/MS/MS, Alkaloids |
description |
Duguetia es un género de plantas perteneciente a la familia Annonaceae. Comprende alrededor de 100 especies, de las cuales, 28 se reportan en regiones pantropicales de Colombia. Varios de sus miembros son reconocidos por sus propiedades antioxidantes. Duguetia vallicola, popularmente conocida como “yaya” es un árbol que crece en el norte de Colombia. De esta especie se han aislado alcaloides de tipo aporfínico en hojas y tallo, con actividad antiplasmodial frente a Plasmodium falciparum. En este trabajo se planteó como objetivo evaluar la composición química del extracto etanólico de la corteza y su actividad antimicrobiana y antioxidante. La metodología consistió inicialmente en una marcha fitoquímica preliminar, para luego continuar con experimentos utilizando cromatografía líquida acoplada a espectrometría de masas (UHPLC-QTof-MS/MS). La actividad antioxidante se realizó evaluando la capacidad captadora de radicales libres, utilizando los métodos de DPPH y ABTS. La actividad antimicrobiana se realizó frente a aislados clínicos de Pseudomonas aeruginosa, por el método de microdilución. La evaluación fitoquímica permitió detectar la presencia de alcaloides, esteroides, triterpenoides y flavonoides, mientras que la medición de la actividad antioxidante del extracto presentó resultados satisfactorios frente al radical DPPH● y radical catiónico ABTS con valores de concentración de inhibición media máxima (IC50) 36,712ppm y 19.659 ppm respectivamente. Los experimentos por UHPLC-QTof-MS/MS, permitieron construir el perfil químico del extracto de corteza de D. vallicola, mediante las bases de datos Global Natural Products Social (GNPS) y la base de datos IQAMDB (IsoQuinolineand Annonaceous Metabolites Data Base) a partir del cual se construyó una red molecular relacionando la masa de cada uno de los compuestos |
publishDate |
2024 |
dc.date.accessioned.none.fl_str_mv |
2024-08-26T21:30:22Z |
dc.date.available.none.fl_str_mv |
2024-08-26T21:30:22Z 2025-08-26 |
dc.date.issued.none.fl_str_mv |
2024-08-26 |
dc.type.none.fl_str_mv |
Trabajo de grado - Pregrado |
dc.type.driver.none.fl_str_mv |
info:eu-repo/semantics/bachelorThesis |
dc.type.coar.none.fl_str_mv |
http://purl.org/coar/resource_type/c_7a1f |
dc.type.version.none.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
dc.type.content.none.fl_str_mv |
Text |
format |
http://purl.org/coar/resource_type/c_7a1f |
status_str |
acceptedVersion |
dc.identifier.uri.none.fl_str_mv |
https://repositorio.unicordoba.edu.co/handle/ucordoba/8645 |
dc.identifier.instname.none.fl_str_mv |
Universidad de Córdoba |
dc.identifier.reponame.none.fl_str_mv |
Repositorio Universidad de Córdoba |
dc.identifier.repourl.none.fl_str_mv |
https://repositorio.unicordoba.edu.co/ |
url |
https://repositorio.unicordoba.edu.co/handle/ucordoba/8645 https://repositorio.unicordoba.edu.co/ |
identifier_str_mv |
Universidad de Córdoba Repositorio Universidad de Córdoba |
dc.language.iso.none.fl_str_mv |
spa |
language |
spa |
dc.relation.references.none.fl_str_mv |
Alves, D. S., Costa, V. A., Machado, A. R. T., Oliveira, D. F., & Carvalho, G. A. (2020). Duguetia lanceolata A. St.-Hil. Stem bark produces phenylpropanoids lethal to Spodoptera frugiperda (JE Smith) (Lepidoptera: Noctuidae). Crop Protection, 127. https://doi.org/10.1016/j.cropro.2019.104965 Arango, O., Pérez, E., Granados, H., Rojano, B., & Sáez, J. (2004). inhibición de la peroxidación lipídica y capacidad atrapadora de radicales libres de alcaloides aislados de dos annonaceae, Xylopia amazonica cf. Y Duguetia vallicola inhibition of the lipid peroxidation and free radical scavenging capacity of alkaloids isolated from two annonaceae, Xylopia amazonica cf. AND Duguetia vallicola. In Actual Biol (Vol. 26, Issue 81). Boruta, T. (2021). A bioprocess perspective on the production of secondary metabolites by Streptomyces in submerged co-cultures. In World Journal of Microbiology and Biotechnology (Vol. 37, Issue 10). Springer Science and Business Media B.V. https://doi.org/10.1007/s11274-021-03141-z Brand-Williams, W., Cuvelier, M. E., & Berset, C. (1995). Use of a Free Radical Method to Evaluate Antioxidant Activity (Vol. 28). Brastianos, H. C., Sturgeon, C. M., Roberge, M., & Andersen, R. J. (2007). Inhibition of the G2 DNA damage checkpoint by oliveroline isolated from Duguetia odorata. Journal of Natural Products, 70(2), 287–288. https://doi.org/10.1021/np060285e Bévalot, F., L. M., & C. A. (1976). Pachypodanthine, a new aporphine alkaloid from pachypodanthium-staudtii engl and diels, Annonaceae. 17, 865–868. Carollo, C. A., De Siqueira, J. M., Garcez, W. S., Diniz, R., & Fernandes, N. G. (2006). N-Nitrosoanonaine and N-nitrosoxylopine, aporphine alkaloids from Duguetia furfuracea. Journal of Natural Products, 69(8), 1222–1224. https://doi.org/10.1021/np0600191 Casagrande, C. & G. F. (1970). tudies in aporphine alkaloids 1. Alkaloids of a Brazilian Duguetia. Farmaco 25(6), 442-448 Cavé, A., Kunesch, N., Leboeuf, M., Bévalot, F., Chiaroni, A., & Riche, C, A. (1980). Alcaloides des annonacees XXV: la staudine, nouvel alcaloide isoquinoleique du Pachypodanthium staudtii Engl. et Diels. Journal of Natural Products, 41, 103–111. Cave, A. (1985). The Chemistry and Biology of Isoquinoline Alkaloids - Annonaceae Alkaloids. In The Chemistry and Biology of Isoquinoline Alkaloids (pp. 79–101). Dantas, E. P., Monteiro, J., de Medeiros, L. S., Romanelli, M. M., Amaral, M., Tempone, A. G., Lago, J. H. G., Soares, M. G., & Sartorelli, P. (2020). Dereplication of Aporphine Alkaloids by UHPLC-HR-ESI-MS/MS and NMR from Duguetia lanceolata St.-Hil (Annonaceae) and Antiparasitic Activity Evaluation. Journal of the Brazilian Chemical Society, 31(9), 1908–1916. https://doi.org/10.21577/0103-5053.20200089 Debourges, D., Roblot, F., Hocquemiller, R., & Cavé, A. (1987). Alcaloïdes des Annonacées, 77. Alcaloïdes de Duguetia spixiana. Journal of Natural Products, 50(4), 664-673. do Santos, R. C., de Souza, A. V., Andrade-Silva, M., Vera Cruz, karoliny C., Leite Kassuya, C. A., Lima Cardoso, C. A., Vieira, M. do C., & Nazari Formagio, A. S. (2018). Antioxidant, anti-rheumatic and anti-inflammatory investigation of extract and dicentrinone from Duguetia furfuracea (A. St.-Hil.) Benth. & Hook. f. Journal of Ethnopharmacology, 211, 9–16. https://doi.org/10.1016/j.jep.2017.09.019 Domingues, V. de C., Ribeiro, L. do P., Gonçalves, G. L. P., Forim, M. R., da Silva, M. F. das G. F., Fernandes, J. B., & Vendramim, J. D. (2020). Grain-protectant compounds from Duguetia lanceolata (Annonaceae) derivatives: Bioassay-guided searching and toxicity against the maize weevil. Journal of Stored Products Research, 85. https://doi.org/10.1016/j.jspr.2019.101549 Eduardo Costa Vieira Lemos, D., Henrique Agra Cavalcante-Silva, L., de Almeida Lima, É., Francisco Alves, A., Silvia Suassuna Carneiro Lúcio, A., Maria Barbosa-Filho, J., & Rodrigues Mascarenhas, S. (2017). Anti-inflammatory Effect of Discretamine, a Protoberberine Alkaloid Isolated from Duguetia moricandiana. Fuentes, L. L., Contreras, O. I., Angulo, A. A., & Contreras M, O. I. (2021). Evaluation of in vitro antioxidant activity of extracts from Duguetia vallicola j.f. Macbr. Annonaceae (Vol. 1, Issue 1). Fechine, I. M., Lima, M. A., Navarro, V. R., Da Cunha, E. V. L., Silva, M. S., Barbosa-Filho, J. M., & Maia, J. G. S. (2002). Alcalóides de Duguetia trunciflora Maas (Annonaceae). Revista Brasileira de Farmacognosia, 12, 17-19 Gilbert, M. T. (1987). Introduction. In High Performance Liquid Chromatography (pp. 1–4). Elsevier. https://doi.org/10.1016/B978-0-7236-0897-4.50007-0 J. Orlando Rangel Ch. (2012). COLOMBIA DIVERSIDAD BIÓTICA XII La región Caribe de Colombia. Kitson, F. G., Larsen, B. S., & McEwen, C. N. (1996). What Is GC/MS Gas Chromatography and Mass Spectrometry, 3–23. https://doi.org/10.1016/B978-012483385-2/50002-6 Kwiek, J. J., Haystead, T. A. J., & Rudolph, J. (2004). Kinetic Mechanism of Quinone Oxidoreductase 2 and Its Inhibition by the Antimalarial Quinolines. Biochemistry, 43(15), 4538–4547. https://doi.org/10.1021/bi035923w Almeida, J. R. G. S., De Lima, J. T., De Oliveira, H. R., De Oliveira, M. R., Meira, P. R. M., Lcio, A. S. S. C., Barbosa Filho, J. M., & Quintans Jnior, L. J. (2011). Antinociceptive activity of discretamine isolated from Duguetia moricandiana. Natural Product Research, 25(20), 1908–1915. https://doi.org/10.1080/14786419.2010.491227 Leboeuf, M., Cave, A., Bhaumik, P. K., Mukherjee, B., & Mukherjeets, R. (1982). THE PHYTOCHEMISTRY OF THE ANNONACEAE. In Phytochemistry (Vol. 21, Issue 12). Lúcio, A. S. S. C., Almeida, J. R. G. da S., da-Cunha, E. V. L., Tavares, J. F., & Barbosa Filho, J. M. (2015). Alkaloids of the Annonaceae: Occurrence and a Compilation of Their Biological Activities. Alkaloids: Chemistry and Biology, 74, 233–409. https://doi.org/10.1016/bs.alkal.2014.09.002 Maas, P. J. M. (2003). Duguetia (Annonaceae). Published for Organization for Flora Neotropica by the New York Botanical Garden. Maas, P. J. M., Westra, L. Y. T., Rainer, H., Lobão, A. Q., & Erkens, R. H. J. (2011). An updated index to genera, species, and infraspecific taxa of Neotropical Annonaceae. Nordic Journal of Botany, 29(3), 257–356. https://doi.org/10.1111/j.1756-1051.2011.01092.x Martha Lucia Ruiz Benitez. (2022). Guía de Determinación de la actividad antioxidante. (Guía de laboratorio). Universidad Simón Bolívar. Mathouet, H., Elomri, A., Lameiras, P., Daïch, A., & Vérité, P. (2007). An alkaloid, two conjugate sesquiterpenes and a phenylpropanoid from Pachypodanthium confine Engl. and Diels. Phytochemistry, 68(13), 1813–1818. https://doi.org/10.1016/j.phytochem.2007.04.001 Fuentes, L. L. M. (2020). Química del género Duguetia (Annonaceae). (Proyecto de grado). Universidad de Córdoba, Colombia. Mijares S., F. J., Aymard C., G. A., & Pérez Buitrago, N. (2018). New records for the vascular flora of Colombia present in the Orinoquia and historical review of botanical expeditions to the region. Biota Colombiana, 18(2), 73–88. https://doi.org/10.21068/c2017.v18n02a05 Ngouonpe, A. W., Mbobda, A. S. W., Happi, G. M., Mbiantcha, M., Tatuedom, O. K., Ali, M. S., Lateef, M., Tchouankeu, J. C., & Kouam, S. F. (2019). Natural products from the medicinal plant Duguetia staudtii (Annonaceae). Biochemical Systematics and Ecology, 83, 22–25. https://doi.org/10.1016/j.bse.2018.12.015 Organizacion mundual de la salud OMS. (2023). Primera Cumbre Mundial de la OMS sobre Medicina Tradicional. Https://Www.Who.Int/Es/News-Room/Events/Detail/2023/08/17/Default-Calendar/the-First-Who-Traditional-Medicine-Global-Summit. Organización panamericana de la salud. (n.d.). glosario microorganismo. Https://Www3.Paho.Org/Hq/Index.Php?Option=com_content&view=article&id=10556:2015-Glosario&Itemid=0&lang=es#gsc.Tab=0. Pachaiappan, R., Nagasathiya, K., Singh, P. K., Gopalakrishnan, A. V., Velusamy, P., Ramasamy, K., Velmurugan, D., Kandasamy, R., Ramasamy, P., & Gopinath, S. C. B. (2022). Phytochemical profile of black cumin (Nigella sativa L.) seed oil: identification of bioactive anti-pathogenic compounds for traditional Siddha formulation. Biomass Conversion and Biorefinery. https://doi.org/10.1007/s13399-022-02951-x Paz, W. H. P., De Oliveira, R. N., Heerdt, G., Angolini, C. F. F., S. De Medeiros, L., Silva, V. R., Santos, L. S., Soares, M. B. P., Bezerra, D. P., Morgon, N. H., Almeida, J. R. G. S., Da Silva, F. M. A., Costa, E. V., & Koolen, H. H. F. (2019). Structure-Based Molecular Networking for the Target Discovery of Oxahomoaporphine and 8-Oxohomoaporphine Alkaloids from Duguetia surinamensis. Journal of Natural Products, 82(8), 2220–2228. https://doi.org/10.1021/acs.jnatprod.9b00287 Pérez, E. G., & Cassels, B. K. (2010). Alkaloids from the Genus Duguetia. In Alkaloids: Chemistry and Biology (Vol. 68, pp. 83–156). Academic Press Inc. https://doi.org/10.1016/S1099-4831(10)06803-3 Pérez, E. G., Sáez, J., & Cassels, B. K. (2005). A convenient, renewable source of the anxiolytic proaporphine alkaloid glaziovine: Duguetia vallicola leaves. Journal of the Chilean Chemical Society, 50(3), 45–53. https://doi.org/10.4067/s0717-97072005000300005 Pérez, E., Sáez, J., Blair, S., Franck, X., & Figadère, B. (2004). Isoquinoline Alkaloids from Duguetia Vallicola Stem Bark with Antiplasmodial Activity. In Letters in Organic Chemistry (Vol. 1). Rafaela Campostrini Forzza. (2010). Catálogo de plantas e fungos do Brasil. http://books.scielo.org Roblot, F., Hocquemiller, R., & Cave, A. (1983a). ALCALOIDES DES ANNONACEES, XLIV. ALCALOIDES DE Duguetia obovata. In Journal of Natural Product (Vol. 46, Issue 6). Venkateswaran, V., Muralidharan, S., Gopalakrishnan, A. V., Krishnan, N., Velmurugan, D., & Raman, P. (2022). GC - MS analysis of guttation fluids from selected crop plants. Journal of Crop Improvement, 36(6), 801–815. https://doi.org/10.1080/15427528.2021.2018748 Weber, C., & Opatz, T. (2019). Bisbenzylisoquinoline Alkaloids. In Alkaloids: Chemistry and Biology (Vol. 81, pp. 1–114). Academic Press Inc. https://doi.org/10.1016/bs.alkal.2018.07.001 Zeliger, H. I. (2023). Introduction. Oxidative Stress, 3–5. https://doi.org/10.1016/B978-0-323-91890-9.00031-3 ADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY Lúcio, A. S. S. C., Almeida, J. R. G. da S., da-Cunha, E. V. L., Tavares, J. F., & Barbosa Filho, J. M. (2015). Alkaloids of the Annonaceae: Occurrence and a Compilation of Their Biological Activities. Alkaloids: Chemistry and Biology, 74, 233–409. https://doi.org/10.1016/bs.alkal.2014.09.002 Castro-Moreno, M., & Rosa González-Esquinca, A. (2016). La familia Annonaceae Juss. en México. 10, 71–82. www.mnh.si.edu Dantas, E. P., Monteiro, J., de Medeiros, L. S., Romanelli, M. M., Amaral, M., Tempone, A. G., Lago, J. H. G., Soares, M. G., & Sartorelli, P. (2020). Dereplication of Aporphine Alkaloids by UHPLC-HR-ESI-MS/MS and NMR from Duguetia lanceolata St.-Hil (Annonaceae) and Antiparasitic Activity Evaluation. Journal of the Brazilian Chemical Society, 31(9), 1908–1916. https://doi.org/10.21577/0103-5053.20200089 Lima, B. R., Lima, J. M., Maciel, J. B., Valentim, C. Q., Nunomura, R. de C. S., Lima, E. S., Koolen, H. H. F., de Souza, A. D. L., Pinheiro, M. L. B., Cass, Q. B., & da Silva, F. M. A. (2019). Synthesis and Inhibition Evaluation of New Benzyltetrahydroprotoberberine Alkaloids Designed as Acetylcholinesterase Inhibitors. Frontiers in Chemistry, 7. https://doi.org/10.3389/fchem.2019.00629 Livia Melo Arruda Cunha. (2009). Estudo Fitoquímico e Biológico de Duguetia riparia (Annonaceae)S. Lúcio, A. S. S. C., Almeida, J. R. G. da S., da-Cunha, E. V. L., Tavares, J. F., & Barbosa Filho, J. M. (2015). Alkaloids of the Annonaceae: Occurrence and a Compilation of Their Biological Activities. Alkaloids: Chemistry and Biology, 74, 233–409. https://doi.org/10.1016/bs.alkal.2014.09.002 OMS. (2021). μg/mL OMS. (2023). Primera Cumbre Mundial de la OMS sobre Medicina Tradicional. https://www.who.int/es/news-room/events/detail/2023/08/17/default-calendar/the-first-who-traditional-medicine-global-summit OPS/OMS. (2018). OPS reafirma la importancia de la medicina tradicional para avanzar hacia la salud universal. https://www3.paho.org/hq/index.php?option=com_content&view=article&id=14382:paho-reaffirms-the-importance-of-traditional-medicine-to-advance-towards-universal-health&Itemid=0&lang=es#gsc.tab=0 Organización mundial de la salud. (2020, August 13). Resistencia a los antimicrobianos. https://www.who.int/es/news-room/fact-sheets/detail/antimicrobial-resistance#:~:text=La%20OMS%20ha%20declarado%20que,la%20aparici%C3%B3n%20de%20pat%C3%B3genos%20farmacorresistentes. Universidad de Málaga/SCAI. (2022). Espectrometría de Masas. área de análisis Químico y caracterización de Materiales. https://www.scai.uma.es/areas/aqcm/ems/ems.html Agnès, S. A., Okpekon, T., Kouadio, Y. A., Jagora, A., Bréard, D., Costa, E. V., da Silva, F. M. A., Koolen, H. H. F., Le Ray-Richomme, A. M., Richomme, P., Champy, P., Beniddir, M. A., & Le Pogam, P. (2022). Implementation of a MS/MS database for isoquinoline alkaloids and other annonaceous metabolites. Scientific Data, 9(1). https://doi.org/10.1038/s41597-022-01345-y Alvarez-Rivera, G., Ballesteros-Vivas, D., Parada-Alfonso, F., Ibañez, E., & Cifuentes, A. (2019). Recent applications of high resolution mass spectrometry for the characterization of plant natural products. In TrAC - Trends in Analytical Chemistry (Vol. 112, pp. 87–101). Elsevier B.V. https://doi.org/10.1016/j.trac.2019.01.002 Britto, A. C. S., De Oliveira, A. C. A., Henriques, R. M., Cardoso, G. M. B., Bomfim, D. S., Carvalho, A. A., Moraes, M. O., Pessoa, C., Pinheiro, M. L. B., Costa, E. V., & Bezerra, D. P. (2012). In vitro and in vivo antitumor effects of the essential oil from the leaves of guatteria friesiana. Planta Medica, 78(5), 409–414. https://doi.org/10.1055/s-0031-1298173 Carvajal, C. C. (2019). REVISTA MEDICINA LEGAL DE COSTA RICA ESPECIES REACTIVAS DEL OXÍGENO: FORMACIÓN, FUNCION Y ESTRÉS OXIDATIVO REACTIVE OXYGEN SPECIES: TRAINING, FUNCTION AND OXIDATIVE STRESS. 36(1). Castañeda-Garzón, S. L., Ligarreto M., G. A., & Miranda-Lasprilla, D. (2016). Evaluación morfológica de una colección in situ de species de la familia Annonaceae en Colombia. Agronomia Colombiana, 34(2), 131–140. https://doi.org/10.15446/agron.colomb.v34n2.54527 Costa, R. G. A., Anunciação, T. A. da, Araujo, M. de S., Souza, C. A., Dias, R. B., Sales, C. B. S., Rocha, C. A. G., Soares, M. B. P., Silva, F. M. A. da, Koolen, H. H. F., Costa, E. V., & Bezerra, D. P. (2020). In vitro and in vivo growth inhibition of human acute promyelocytic leukemia HL-60 cells by Guatteria megalophylla Diels (Annonaceae) leaf essential oil. Biomedicine and Pharmacotherapy, 122. https://doi.org/10.1016/j.biopha.2019.109713 Dantas, E. P., Monteiro, J., de Medeiros, L. S., Romanelli, M. M., Amaral, M., Tempone, A. G., Lago, J. H. G., Soares, M. G., & Sartorelli, P. (2020). Dereplication of Aporphine Alkaloids by UHPLC-HR-ESI-MS/MS and NMR from Duguetia lanceolata St.-Hil (Annonaceae) and Antiparasitic Activity Evaluation. Journal of the Brazilian Chemical Society, 31(9), 1908–1916. https://doi.org/10.21577/0103-5053.20200089 Garagounis, C., Delkis, N., & Papadopoulou, K. K. (2021). Unraveling the roles of plant specialized metabolites: using synthetic biology to design molecular biosensors. In New Phytologist (Vol. 231, Issue 4, pp. 1338–1352). John Wiley and Sons Inc. https://doi.org/10.1111/nph.17470 Gomes, P., Quirós-Guerrero, L., Silva, C., Pamplona, S., Boutin, J. A., Eberlin, M., Wolfender, J. L., & Silva, M. (2021). Feature-based molecular network-guided dereplication of natural bioactive products from leaves of stryphnodendron pulcherrimum (Willd.) hochr. Metabolites, 11(5). https://doi.org/10.3390/metabo11050281 I.P.N.I. (2021, May 24). The Royal Botanic Gardens, Kew, Harvard University Herbaria & Libraries e Australian National Botanic Gardens, 2021. Http://Www.Ipni.Org. Jeniferde carvalho lopes, renato mello-silva. (2014). DIVERSIDADE E CARACTERIZAÇÃO DAS ANNONACEAE DO BRASIL 1 (Vol. 36). Kachlicki, P., Piasecka, A., Stobiecki, M., & Marczak, Ł. (2016). Structural characterization of flavonoid glycoconjugates and their derivatives with mass spectrometric techniques. In Molecules (Vol. 21, Issue 11). MDPI AG. https://doi.org/10.3390/molecules21111494 León-Méndez, Glicerio, ;, Pájaro-Castro, Nerlis, ;, & Granados-Conde, C. (2020). Annonaceae squamosa una fuente de acetogeninas en la actualidad Annonaceae squamosa a source of acetogenins today. Ciencia y Salud Virtual, 12(2), 88–101. https://doi.org/10.22519/21455333.1289 Liu, R., Chou, J., Hou, S., Liu, X., Yu, J., Zhao, X., Li, Y., Liu, L., & Sun, C. (2018). Evaluation of two-step liquid-liquid extraction protocol for untargeted metabolic profiling of serum samples to achieve broader metabolome coverage by UPLC-Q-TOF-MS. Analytica Chimica Acta, 1035, 96–107. https://doi.org/10.1016/j.aca.2018.07.034 Livia Melo Arruda Cunha. (2009). Estudo Fitoquímico e Biológico de Duguetia riparia (Annonaceae)S. Lobão, A. Q. , L. J. C. , E. R. H. J. , M.-S. I. , P. P. A. F. , S. L. V. , O. M. L. B. , J. D. , M. R. (2020). Annonaceae in Flora do Brasil 2020. Jardim Botânico do Rio de Janeiro. : : Http:// Floradobrasil.Jbrj.Gov.Br/Reflora/Floradobrasil/FB110219. Lúcio, A. S. S. C., Almeida, J. R. G. da S., da-Cunha, E. V. L., Tavares, J. F., & Barbosa Filho, J. M. (2015). Alkaloids of the Annonaceae: Occurrence and a Compilation of Their Biological Activities. Alkaloids: Chemistry and Biology, 74, 233–409. https://doi.org/10.1016/bs.alkal.2014.09.002 Michopoulos, F., Gika, H., Palachanis, D., Theodoridis, G., & Wilson, I. D. (2015). Solid phase extraction methodology for UPLC-MS based metabolic profiling of urine samples. Electrophoresis, 36(18), 2170–2178. https://doi.org/10.1002/elps.201500101 Murillo, J. (2001). Las Annonaceae de Colombia. In Biota Colombiana (Vol. 2, Issue 1). Nothias, L. F., Petras, D., Schmid, R., Dührkop, K., Rainer, J., Sarvepalli, A., Protsyuk, I., Ernst, M., Tsugawa, H., Fleischauer, M., Aicheler, F., Aksenov, A. A., Alka, O., Allard, P. M., Barsch, A., Cachet, X., Caraballo-Rodriguez, A. M., Da Silva, R. R., Dang, T., … Dorrestein, P. C. (2020). Feature-based molecular networking in the GNPS analysis environment. Nature Methods, 17(9), 905–908. https://doi.org/10.1038/s41592-020-0933-6 Paul J. M. Maas, L. Y. Th. W. L. W. C. (2003). Duguetia (Annonaceae). Published for Organization for Flora Neotropica by the New York Botanical Garden Paz, W. H. P., De Oliveira, R. N., Heerdt, G., Angolini, C. F. F., S. De Medeiros, L., Silva, V. R., Santos, L. S., Soares, M. B. P., Bezerra, D. P., Morgon, N. H., Almeida, J. R. G. S., Da Silva, F. M. A., Costa, E. V, & Koolen, H. H. F. (2019). Structure-Based Molecular Networking for the Target Discovery of Oxahomoaporphine and 8-Oxohomoaporphine Alkaloids from Duguetia surinamensis. Journal of Natural Products, 82(8), 2220–2228. https://doi.org/10.1021/acs.jnatprod.9b00287 Silva, A. F., Rabelo, M. F. R., & Enoque, M. M. (2015). Diversidade de angiospermas e espécies medicinais de uma área de Cerrado. Revista Brasileira de Plantas Medicinais, 17(4), 1016–1030. https://doi.org/10.1590/1983-084X/14_115 Tilvi, S., Majik, M. S., & Singh, K. S. (2014). Mass spectrometry for determination of bioactive compounds. In Comprehensive Analytical Chemistry (Vol. 65, pp. 193–218). Elsevier B.V. https://doi.org/10.1016/B978-0-444-63359-0.00008-2 Wang, S., Alseekh, S., Fernie, A. R., & Luo, J. (2019). The Structure and Function of Major Plant Metabolite Modifications. In Molecular Plant (Vol. 12, Issue 7, pp. 899–919). Cell Press. https://doi.org/10.1016/j.molp.2019.06.001 Wolfender, J. L., Queiroz, E. F., & Hostettmann, K. (2006). The importance of hyphenated techniques in the discovery of new lead compounds from nature. In Expert Opinion on Drug Discovery (Vol. 1, Issue 3, pp. 237–260). https://doi.org/10.1517/17460441.1.3.237 Xue, B., Guo, X., Landis, J. B., Sun, M., Tang, C. C., Soltis, P. S., & Soltis, D. E. (2020). Molecular Phylogenetics and Evolution Accelerated diversification correlated with functional traits shapes extant diversity of the early divergent angiosperm family Annonaceae. Molecular Phylogenetics and Evolution, 142(July 2019), 106659. https://doi.org/10.1016/j.ympev.2019.106659 Zhang, A., Sun, H., & Wang, X. (2018). Mass spectrometry-driven drug discovery for development of herbal medicine. In Mass Spectrometry Reviews (Vol. 37, Issue 3, pp. 307–320). John Wiley and Sons Inc. https://doi.org/10.1002/mas.21529 Zhang, A., Sun, H., Yan, G., & Wang, X. (2017). Recent developments and emerging trends of mass spectrometry for herbal ingredients analysis. In TrAC - Trends in Analytical Chemistry (Vol. 94, pp. 70–76). Elsevier B.V. https://doi.org/10.1016/j.trac.2017.07.007 |
dc.rights.none.fl_str_mv |
Copyright Universidad de Córdoba, 2024 |
dc.rights.uri.none.fl_str_mv |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.rights.license.none.fl_str_mv |
Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0) |
dc.rights.accessrights.none.fl_str_mv |
info:eu-repo/semantics/embargoedAccess |
dc.rights.coar.none.fl_str_mv |
http://purl.org/coar/access_right/c_f1cf |
rights_invalid_str_mv |
Copyright Universidad de Córdoba, 2024 https://creativecommons.org/licenses/by-nc-nd/4.0/ Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0) http://purl.org/coar/access_right/c_f1cf |
eu_rights_str_mv |
embargoedAccess |
dc.format.mimetype.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidad de Córdoba |
dc.publisher.faculty.none.fl_str_mv |
Facultad de Ciencias Básicas |
dc.publisher.place.none.fl_str_mv |
Montería, Córdoba, Colombia |
dc.publisher.program.none.fl_str_mv |
Química |
publisher.none.fl_str_mv |
Universidad de Córdoba |
institution |
Universidad de Córdoba |
bitstream.url.fl_str_mv |
https://repositorio.unicordoba.edu.co/bitstreams/2d491d22-93a1-40c6-88f8-673a2d7606ae/download https://repositorio.unicordoba.edu.co/bitstreams/e929fcc2-2b19-4741-870b-d8a4378fcb25/download https://repositorio.unicordoba.edu.co/bitstreams/9e61af65-571e-40d0-8eb7-bb8056d732e3/download https://repositorio.unicordoba.edu.co/bitstreams/4f9b6a25-9d74-4d2b-a38f-4ffafcb20aa3/download https://repositorio.unicordoba.edu.co/bitstreams/3515ec5a-5a52-4ae5-a80d-1be0d40e28d1/download https://repositorio.unicordoba.edu.co/bitstreams/5b125446-b819-492b-9e5d-808dd3ff9f7f/download https://repositorio.unicordoba.edu.co/bitstreams/7ae3fec2-6e63-47c7-8380-45ecd82ea50e/download |
bitstream.checksum.fl_str_mv |
73a5432e0b76442b22b026844140d683 9b2bef764375f448a6cb94c223c3f6aa e1b611cde46307c2cd32fef368a960d5 bca2665cb1a845518fb61e422847827e d5b4dad4fa551bfa00ffedeb17697cff 149b6ab207f84b5456a77aea79858f6d eb0150d01bf04c7d6dc29bb3e77161f2 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositorio Universidad de Córdoba |
repository.mail.fl_str_mv |
bdigital@metabiblioteca.com |
_version_ |
1839636165503746048 |
spelling |
Angulo Ortiz, Alberto Antonioc883b19e-071c-4acd-88b6-25cd468736fd-1Padron Calderon, Jose Raul808cf2c6-a0ff-4c15-acae-d78aad559e8c-1Valle Zapata, Hernan Alonso744348e2-deca-4ed4-9b02-05a6766f4f34-1Marin Severiche, Fernis Joseaeae0399-5fcb-446b-9b14-0125aabb97c7-12024-08-26T21:30:22Z2025-08-262024-08-26T21:30:22Z2024-08-26https://repositorio.unicordoba.edu.co/handle/ucordoba/8645Universidad de CórdobaRepositorio Universidad de Córdobahttps://repositorio.unicordoba.edu.co/Duguetia es un género de plantas perteneciente a la familia Annonaceae. Comprende alrededor de 100 especies, de las cuales, 28 se reportan en regiones pantropicales de Colombia. Varios de sus miembros son reconocidos por sus propiedades antioxidantes. Duguetia vallicola, popularmente conocida como “yaya” es un árbol que crece en el norte de Colombia. De esta especie se han aislado alcaloides de tipo aporfínico en hojas y tallo, con actividad antiplasmodial frente a Plasmodium falciparum. En este trabajo se planteó como objetivo evaluar la composición química del extracto etanólico de la corteza y su actividad antimicrobiana y antioxidante. La metodología consistió inicialmente en una marcha fitoquímica preliminar, para luego continuar con experimentos utilizando cromatografía líquida acoplada a espectrometría de masas (UHPLC-QTof-MS/MS). La actividad antioxidante se realizó evaluando la capacidad captadora de radicales libres, utilizando los métodos de DPPH y ABTS. La actividad antimicrobiana se realizó frente a aislados clínicos de Pseudomonas aeruginosa, por el método de microdilución. La evaluación fitoquímica permitió detectar la presencia de alcaloides, esteroides, triterpenoides y flavonoides, mientras que la medición de la actividad antioxidante del extracto presentó resultados satisfactorios frente al radical DPPH● y radical catiónico ABTS con valores de concentración de inhibición media máxima (IC50) 36,712ppm y 19.659 ppm respectivamente. Los experimentos por UHPLC-QTof-MS/MS, permitieron construir el perfil químico del extracto de corteza de D. vallicola, mediante las bases de datos Global Natural Products Social (GNPS) y la base de datos IQAMDB (IsoQuinolineand Annonaceous Metabolites Data Base) a partir del cual se construyó una red molecular relacionando la masa de cada uno de los compuestosINTRODUCCIONOBJETIVOSOBJETIVO GENERALOBJETIVO ESPECIFICOMARCO TEORICOMETODOLOGIAMUESTRARECOLECCIÓN DE MUESTRA VEGETALELABORACIÓN DE EXTRACTO ETANOLICO DE LA CORTEZA DE DUGUETIA VALLICOLAANÁLISIS Y SEPARACIÓN DE LOS METABOLITOS SECUNDARIOSIDENTIFICACIÓN QUÍMICA DE LOS METABOLITOS SECUNDARIOSPREPARACIÓN DE MUESTRACONDICIONES CROMATOGRÁFICASESPECTROMETRÍA DE MASASEVALUACIÓN DE LA ACTIVIDAD ANTIOXIDANTEMÉTODO DEL RADICAL DPPH (2,2-DIFENIL-1-PICRIL-HIDRAZILO)MÉTODO DE RADICAL CATIÓNICO 2,2-AZINO-BIS-3-ETILBENZTIAZOLIN-6-SULFONATO DE AMONIO (ABTS)EVALUACIÓN DE LA ACTIVIDAD ANTIMICROBIANARESULTADOS Y DISCUSIÓNANALSIS FITOQUIMICOANALSIS CROMATOGRAFICOCROMATOGRAFICO EN PLACA DELGADACROMATOGRAFIA EN COLUMNAANÁLSIS DEL PERFIL QUIMICO DEL EXTRACTO DE Duguetia vallicolaANÁLISIS ESPECTROMETRICOS (LC-MS/MS)ACTIVIDAD ANTIOXIDANTEMETODO POR EL RADICAL DPPH (2,2-Difenil-1-picrihidrazilo)ENSAYO CON RADICAL CATIONICO (2,2’- azino-bis-(3-etilbenztiazolin-6-sulfonato de amonio)) (ABTS)ACTIVIDAD ANTIMICROBIANAPRUEDAD DE SUSCEPTIBILIDADCONCLUSIONESBIBLIOGRAFIAPregradoQuímico(a)Trabajos de Investigación y/o Extensiónapplication/pdfspaUniversidad de CórdobaFacultad de Ciencias BásicasMontería, Córdoba, ColombiaQuímicaCopyright Universidad de Córdoba, 2024https://creativecommons.org/licenses/by-nc-nd/4.0/Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)info:eu-repo/semantics/embargoedAccesshttp://purl.org/coar/access_right/c_f1cfEstudio químico del extracto de la corteza de Dguetia vallicola (Annonaceae), actividad antimicrobiana y antioxidanteTrabajo de grado - Pregradoinfo:eu-repo/semantics/bachelorThesishttp://purl.org/coar/resource_type/c_7a1finfo:eu-repo/semantics/acceptedVersionTextAlves, D. S., Costa, V. A., Machado, A. R. T., Oliveira, D. F., & Carvalho, G. A. (2020). Duguetia lanceolata A. St.-Hil. Stem bark produces phenylpropanoids lethal to Spodoptera frugiperda (JE Smith) (Lepidoptera: Noctuidae). Crop Protection, 127. https://doi.org/10.1016/j.cropro.2019.104965Arango, O., Pérez, E., Granados, H., Rojano, B., & Sáez, J. (2004). inhibición de la peroxidación lipídica y capacidad atrapadora de radicales libres de alcaloides aislados de dos annonaceae, Xylopia amazonica cf. Y Duguetia vallicola inhibition of the lipid peroxidation and free radical scavenging capacity of alkaloids isolated from two annonaceae, Xylopia amazonica cf. AND Duguetia vallicola. In Actual Biol (Vol. 26, Issue 81).Boruta, T. (2021). A bioprocess perspective on the production of secondary metabolites by Streptomyces in submerged co-cultures. In World Journal of Microbiology and Biotechnology (Vol. 37, Issue 10). Springer Science and Business Media B.V. https://doi.org/10.1007/s11274-021-03141-zBrand-Williams, W., Cuvelier, M. E., & Berset, C. (1995). Use of a Free Radical Method to Evaluate Antioxidant Activity (Vol. 28).Brastianos, H. C., Sturgeon, C. M., Roberge, M., & Andersen, R. J. (2007). Inhibition of the G2 DNA damage checkpoint by oliveroline isolated from Duguetia odorata. Journal of Natural Products, 70(2), 287–288. https://doi.org/10.1021/np060285eBévalot, F., L. M., & C. A. (1976). Pachypodanthine, a new aporphine alkaloid from pachypodanthium-staudtii engl and diels, Annonaceae. 17, 865–868. Carollo, C. A., De Siqueira, J. M., Garcez, W. S., Diniz, R., & Fernandes, N. G. (2006). N-Nitrosoanonaine and N-nitrosoxylopine, aporphine alkaloids from Duguetia furfuracea. Journal of Natural Products, 69(8), 1222–1224. https://doi.org/10.1021/np0600191Casagrande, C. & G. F. (1970). tudies in aporphine alkaloids 1. Alkaloids of a Brazilian Duguetia. Farmaco 25(6), 442-448Cavé, A., Kunesch, N., Leboeuf, M., Bévalot, F., Chiaroni, A., & Riche, C, A. (1980). Alcaloides des annonacees XXV: la staudine, nouvel alcaloide isoquinoleique du Pachypodanthium staudtii Engl. et Diels. Journal of Natural Products, 41, 103–111.Cave, A. (1985). The Chemistry and Biology of Isoquinoline Alkaloids - Annonaceae Alkaloids. In The Chemistry and Biology of Isoquinoline Alkaloids (pp. 79–101).Dantas, E. P., Monteiro, J., de Medeiros, L. S., Romanelli, M. M., Amaral, M., Tempone, A. G., Lago, J. H. G., Soares, M. G., & Sartorelli, P. (2020). Dereplication of Aporphine Alkaloids by UHPLC-HR-ESI-MS/MS and NMR from Duguetia lanceolata St.-Hil (Annonaceae) and Antiparasitic Activity Evaluation. Journal of the Brazilian Chemical Society, 31(9), 1908–1916. https://doi.org/10.21577/0103-5053.20200089Debourges, D., Roblot, F., Hocquemiller, R., & Cavé, A. (1987). Alcaloïdes des Annonacées, 77. Alcaloïdes de Duguetia spixiana. Journal of Natural Products, 50(4), 664-673.do Santos, R. C., de Souza, A. V., Andrade-Silva, M., Vera Cruz, karoliny C., Leite Kassuya, C. A., Lima Cardoso, C. A., Vieira, M. do C., & Nazari Formagio, A. S. (2018). Antioxidant, anti-rheumatic and anti-inflammatory investigation of extract and dicentrinone from Duguetia furfuracea (A. St.-Hil.) Benth. & Hook. f. Journal of Ethnopharmacology, 211, 9–16. https://doi.org/10.1016/j.jep.2017.09.019Domingues, V. de C., Ribeiro, L. do P., Gonçalves, G. L. P., Forim, M. R., da Silva, M. F. das G. F., Fernandes, J. B., & Vendramim, J. D. (2020). Grain-protectant compounds from Duguetia lanceolata (Annonaceae) derivatives: Bioassay-guided searching and toxicity against the maize weevil. Journal of Stored Products Research, 85. https://doi.org/10.1016/j.jspr.2019.101549Eduardo Costa Vieira Lemos, D., Henrique Agra Cavalcante-Silva, L., de Almeida Lima, É., Francisco Alves, A., Silvia Suassuna Carneiro Lúcio, A., Maria Barbosa-Filho, J., & Rodrigues Mascarenhas, S. (2017). Anti-inflammatory Effect of Discretamine, a Protoberberine Alkaloid Isolated from Duguetia moricandiana.Fuentes, L. L., Contreras, O. I., Angulo, A. A., & Contreras M, O. I. (2021). Evaluation of in vitro antioxidant activity of extracts from Duguetia vallicola j.f. Macbr. Annonaceae (Vol. 1, Issue 1).Fechine, I. M., Lima, M. A., Navarro, V. R., Da Cunha, E. V. L., Silva, M. S., Barbosa-Filho, J. M., & Maia, J. G. S. (2002). Alcalóides de Duguetia trunciflora Maas (Annonaceae). Revista Brasileira de Farmacognosia, 12, 17-19Gilbert, M. T. (1987). Introduction. In High Performance Liquid Chromatography (pp. 1–4). Elsevier. https://doi.org/10.1016/B978-0-7236-0897-4.50007-0J. Orlando Rangel Ch. (2012). COLOMBIA DIVERSIDAD BIÓTICA XII La región Caribe de Colombia.Kitson, F. G., Larsen, B. S., & McEwen, C. N. (1996). What Is GC/MS Gas Chromatography and Mass Spectrometry, 3–23. https://doi.org/10.1016/B978-012483385-2/50002-6Kwiek, J. J., Haystead, T. A. J., & Rudolph, J. (2004). Kinetic Mechanism of Quinone Oxidoreductase 2 and Its Inhibition by the Antimalarial Quinolines. Biochemistry, 43(15), 4538–4547. https://doi.org/10.1021/bi035923wAlmeida, J. R. G. S., De Lima, J. T., De Oliveira, H. R., De Oliveira, M. R., Meira, P. R. M., Lcio, A. S. S. C., Barbosa Filho, J. M., & Quintans Jnior, L. J. (2011). Antinociceptive activity of discretamine isolated from Duguetia moricandiana. Natural Product Research, 25(20), 1908–1915. https://doi.org/10.1080/14786419.2010.491227Leboeuf, M., Cave, A., Bhaumik, P. K., Mukherjee, B., & Mukherjeets, R. (1982). THE PHYTOCHEMISTRY OF THE ANNONACEAE. In Phytochemistry (Vol. 21, Issue 12).Lúcio, A. S. S. C., Almeida, J. R. G. da S., da-Cunha, E. V. L., Tavares, J. F., & Barbosa Filho, J. M. (2015). Alkaloids of the Annonaceae: Occurrence and a Compilation of Their Biological Activities. Alkaloids: Chemistry and Biology, 74, 233–409. https://doi.org/10.1016/bs.alkal.2014.09.002Maas, P. J. M. (2003). Duguetia (Annonaceae). Published for Organization for Flora Neotropica by the New York Botanical Garden.Maas, P. J. M., Westra, L. Y. T., Rainer, H., Lobão, A. Q., & Erkens, R. H. J. (2011). An updated index to genera, species, and infraspecific taxa of Neotropical Annonaceae. Nordic Journal of Botany, 29(3), 257–356. https://doi.org/10.1111/j.1756-1051.2011.01092.xMartha Lucia Ruiz Benitez. (2022). Guía de Determinación de la actividad antioxidante. (Guía de laboratorio). Universidad Simón Bolívar.Mathouet, H., Elomri, A., Lameiras, P., Daïch, A., & Vérité, P. (2007). An alkaloid, two conjugate sesquiterpenes and a phenylpropanoid from Pachypodanthium confine Engl. and Diels. Phytochemistry, 68(13), 1813–1818. https://doi.org/10.1016/j.phytochem.2007.04.001Fuentes, L. L. M. (2020). Química del género Duguetia (Annonaceae). (Proyecto de grado). Universidad de Córdoba, Colombia. Mijares S., F. J., Aymard C., G. A., & Pérez Buitrago, N. (2018). New records for the vascular flora of Colombia present in the Orinoquia and historical review of botanical expeditions to the region. Biota Colombiana, 18(2), 73–88. https://doi.org/10.21068/c2017.v18n02a05Ngouonpe, A. W., Mbobda, A. S. W., Happi, G. M., Mbiantcha, M., Tatuedom, O. K., Ali, M. S., Lateef, M., Tchouankeu, J. C., & Kouam, S. F. (2019). Natural products from the medicinal plant Duguetia staudtii (Annonaceae). Biochemical Systematics and Ecology, 83, 22–25. https://doi.org/10.1016/j.bse.2018.12.015Organizacion mundual de la salud OMS. (2023). Primera Cumbre Mundial de la OMS sobre Medicina Tradicional. Https://Www.Who.Int/Es/News-Room/Events/Detail/2023/08/17/Default-Calendar/the-First-Who-Traditional-Medicine-Global-Summit.Organización panamericana de la salud. (n.d.). glosario microorganismo. Https://Www3.Paho.Org/Hq/Index.Php?Option=com_content&view=article&id=10556:2015-Glosario&Itemid=0&lang=es#gsc.Tab=0.Pachaiappan, R., Nagasathiya, K., Singh, P. K., Gopalakrishnan, A. V., Velusamy, P., Ramasamy, K., Velmurugan, D., Kandasamy, R., Ramasamy, P., & Gopinath, S. C. B. (2022). Phytochemical profile of black cumin (Nigella sativa L.) seed oil: identification of bioactive anti-pathogenic compounds for traditional Siddha formulation. Biomass Conversion and Biorefinery. https://doi.org/10.1007/s13399-022-02951-xPaz, W. H. P., De Oliveira, R. N., Heerdt, G., Angolini, C. F. F., S. De Medeiros, L., Silva, V. R., Santos, L. S., Soares, M. B. P., Bezerra, D. P., Morgon, N. H., Almeida, J. R. G. S., Da Silva, F. M. A., Costa, E. V., & Koolen, H. H. F. (2019). Structure-Based Molecular Networking for the Target Discovery of Oxahomoaporphine and 8-Oxohomoaporphine Alkaloids from Duguetia surinamensis. Journal of Natural Products, 82(8), 2220–2228. https://doi.org/10.1021/acs.jnatprod.9b00287Pérez, E. G., & Cassels, B. K. (2010). Alkaloids from the Genus Duguetia. In Alkaloids: Chemistry and Biology (Vol. 68, pp. 83–156). Academic Press Inc. https://doi.org/10.1016/S1099-4831(10)06803-3Pérez, E. G., Sáez, J., & Cassels, B. K. (2005). A convenient, renewable source of the anxiolytic proaporphine alkaloid glaziovine: Duguetia vallicola leaves. Journal of the Chilean Chemical Society, 50(3), 45–53. https://doi.org/10.4067/s0717-97072005000300005Pérez, E., Sáez, J., Blair, S., Franck, X., & Figadère, B. (2004). Isoquinoline Alkaloids from Duguetia Vallicola Stem Bark with Antiplasmodial Activity. In Letters in Organic Chemistry (Vol. 1).Rafaela Campostrini Forzza. (2010). Catálogo de plantas e fungos do Brasil. http://books.scielo.orgRoblot, F., Hocquemiller, R., & Cave, A. (1983a). ALCALOIDES DES ANNONACEES, XLIV. ALCALOIDES DE Duguetia obovata. In Journal of Natural Product (Vol. 46, Issue 6).Venkateswaran, V., Muralidharan, S., Gopalakrishnan, A. V., Krishnan, N., Velmurugan, D., & Raman, P. (2022). GC - MS analysis of guttation fluids from selected crop plants. Journal of Crop Improvement, 36(6), 801–815. https://doi.org/10.1080/15427528.2021.2018748Weber, C., & Opatz, T. (2019). Bisbenzylisoquinoline Alkaloids. In Alkaloids: Chemistry and Biology (Vol. 81, pp. 1–114). Academic Press Inc. https://doi.org/10.1016/bs.alkal.2018.07.001Zeliger, H. I. (2023). Introduction. Oxidative Stress, 3–5. https://doi.org/10.1016/B978-0-323-91890-9.00031-3ADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY Lúcio, A. S. S. C., Almeida, J. R. G. da S., da-Cunha, E. V. L., Tavares, J. F., & Barbosa Filho, J. M. (2015). Alkaloids of the Annonaceae: Occurrence and a Compilation of Their Biological Activities. Alkaloids: Chemistry and Biology, 74, 233–409. https://doi.org/10.1016/bs.alkal.2014.09.002Castro-Moreno, M., & Rosa González-Esquinca, A. (2016). La familia Annonaceae Juss. en México. 10, 71–82. www.mnh.si.eduDantas, E. P., Monteiro, J., de Medeiros, L. S., Romanelli, M. M., Amaral, M., Tempone, A. G., Lago, J. H. G., Soares, M. G., & Sartorelli, P. (2020). Dereplication of Aporphine Alkaloids by UHPLC-HR-ESI-MS/MS and NMR from Duguetia lanceolata St.-Hil (Annonaceae) and Antiparasitic Activity Evaluation. Journal of the Brazilian Chemical Society, 31(9), 1908–1916. https://doi.org/10.21577/0103-5053.20200089Lima, B. R., Lima, J. M., Maciel, J. B., Valentim, C. Q., Nunomura, R. de C. S., Lima, E. S., Koolen, H. H. F., de Souza, A. D. L., Pinheiro, M. L. B., Cass, Q. B., & da Silva, F. M. A. (2019). Synthesis and Inhibition Evaluation of New Benzyltetrahydroprotoberberine Alkaloids Designed as Acetylcholinesterase Inhibitors. Frontiers in Chemistry, 7. https://doi.org/10.3389/fchem.2019.00629Livia Melo Arruda Cunha. (2009). Estudo Fitoquímico e Biológico de Duguetia riparia (Annonaceae)S.Lúcio, A. S. S. C., Almeida, J. R. G. da S., da-Cunha, E. V. L., Tavares, J. F., & Barbosa Filho, J. M. (2015). Alkaloids of the Annonaceae: Occurrence and a Compilation of Their Biological Activities. Alkaloids: Chemistry and Biology, 74, 233–409. https://doi.org/10.1016/bs.alkal.2014.09.002OMS. (2021). μg/mL OMS. (2023). Primera Cumbre Mundial de la OMS sobre Medicina Tradicional. https://www.who.int/es/news-room/events/detail/2023/08/17/default-calendar/the-first-who-traditional-medicine-global-summitOPS/OMS. (2018). OPS reafirma la importancia de la medicina tradicional para avanzar hacia la salud universal. https://www3.paho.org/hq/index.php?option=com_content&view=article&id=14382:paho-reaffirms-the-importance-of-traditional-medicine-to-advance-towards-universal-health&Itemid=0&lang=es#gsc.tab=0Organización mundial de la salud. (2020, August 13). Resistencia a los antimicrobianos. https://www.who.int/es/news-room/fact-sheets/detail/antimicrobial-resistance#:~:text=La%20OMS%20ha%20declarado%20que,la%20aparici%C3%B3n%20de%20pat%C3%B3genos%20farmacorresistentes.Universidad de Málaga/SCAI. (2022). Espectrometría de Masas. área de análisis Químico y caracterización de Materiales. https://www.scai.uma.es/areas/aqcm/ems/ems.htmlAgnès, S. A., Okpekon, T., Kouadio, Y. A., Jagora, A., Bréard, D., Costa, E. V., da Silva, F. M. A., Koolen, H. H. F., Le Ray-Richomme, A. M., Richomme, P., Champy, P., Beniddir, M. A., & Le Pogam, P. (2022). Implementation of a MS/MS database for isoquinoline alkaloids and other annonaceous metabolites. Scientific Data, 9(1). https://doi.org/10.1038/s41597-022-01345-yAlvarez-Rivera, G., Ballesteros-Vivas, D., Parada-Alfonso, F., Ibañez, E., & Cifuentes, A. (2019). Recent applications of high resolution mass spectrometry for the characterization of plant natural products. In TrAC - Trends in Analytical Chemistry (Vol. 112, pp. 87–101). Elsevier B.V. https://doi.org/10.1016/j.trac.2019.01.002Britto, A. C. S., De Oliveira, A. C. A., Henriques, R. M., Cardoso, G. M. B., Bomfim, D. S., Carvalho, A. A., Moraes, M. O., Pessoa, C., Pinheiro, M. L. B., Costa, E. V., & Bezerra, D. P. (2012). In vitro and in vivo antitumor effects of the essential oil from the leaves of guatteria friesiana. Planta Medica, 78(5), 409–414. https://doi.org/10.1055/s-0031-1298173Carvajal, C. C. (2019). REVISTA MEDICINA LEGAL DE COSTA RICA ESPECIES REACTIVAS DEL OXÍGENO: FORMACIÓN, FUNCION Y ESTRÉS OXIDATIVO REACTIVE OXYGEN SPECIES: TRAINING, FUNCTION AND OXIDATIVE STRESS. 36(1).Castañeda-Garzón, S. L., Ligarreto M., G. A., & Miranda-Lasprilla, D. (2016). Evaluación morfológica de una colección in situ de species de la familia Annonaceae en Colombia. Agronomia Colombiana, 34(2), 131–140. https://doi.org/10.15446/agron.colomb.v34n2.54527Costa, R. G. A., Anunciação, T. A. da, Araujo, M. de S., Souza, C. A., Dias, R. B., Sales, C. B. S., Rocha, C. A. G., Soares, M. B. P., Silva, F. M. A. da, Koolen, H. H. F., Costa, E. V., & Bezerra, D. P. (2020). In vitro and in vivo growth inhibition of human acute promyelocytic leukemia HL-60 cells by Guatteria megalophylla Diels (Annonaceae) leaf essential oil. Biomedicine and Pharmacotherapy, 122. https://doi.org/10.1016/j.biopha.2019.109713Dantas, E. P., Monteiro, J., de Medeiros, L. S., Romanelli, M. M., Amaral, M., Tempone, A. G., Lago, J. H. G., Soares, M. G., & Sartorelli, P. (2020). Dereplication of Aporphine Alkaloids by UHPLC-HR-ESI-MS/MS and NMR from Duguetia lanceolata St.-Hil (Annonaceae) and Antiparasitic Activity Evaluation. Journal of the Brazilian Chemical Society, 31(9), 1908–1916. https://doi.org/10.21577/0103-5053.20200089Garagounis, C., Delkis, N., & Papadopoulou, K. K. (2021). Unraveling the roles of plant specialized metabolites: using synthetic biology to design molecular biosensors. In New Phytologist (Vol. 231, Issue 4, pp. 1338–1352). John Wiley and Sons Inc. https://doi.org/10.1111/nph.17470Gomes, P., Quirós-Guerrero, L., Silva, C., Pamplona, S., Boutin, J. A., Eberlin, M., Wolfender, J. L., & Silva, M. (2021). Feature-based molecular network-guided dereplication of natural bioactive products from leaves of stryphnodendron pulcherrimum (Willd.) hochr. Metabolites, 11(5). https://doi.org/10.3390/metabo11050281I.P.N.I. (2021, May 24). The Royal Botanic Gardens, Kew, Harvard University Herbaria & Libraries e Australian National Botanic Gardens, 2021. Http://Www.Ipni.Org.Jeniferde carvalho lopes, renato mello-silva. (2014). DIVERSIDADE E CARACTERIZAÇÃO DAS ANNONACEAE DO BRASIL 1 (Vol. 36).Kachlicki, P., Piasecka, A., Stobiecki, M., & Marczak, Ł. (2016). Structural characterization of flavonoid glycoconjugates and their derivatives with mass spectrometric techniques. In Molecules (Vol. 21, Issue 11). MDPI AG. https://doi.org/10.3390/molecules21111494León-Méndez, Glicerio, ;, Pájaro-Castro, Nerlis, ;, & Granados-Conde, C. (2020). Annonaceae squamosa una fuente de acetogeninas en la actualidad Annonaceae squamosa a source of acetogenins today. Ciencia y Salud Virtual, 12(2), 88–101. https://doi.org/10.22519/21455333.1289Liu, R., Chou, J., Hou, S., Liu, X., Yu, J., Zhao, X., Li, Y., Liu, L., & Sun, C. (2018). Evaluation of two-step liquid-liquid extraction protocol for untargeted metabolic profiling of serum samples to achieve broader metabolome coverage by UPLC-Q-TOF-MS. Analytica Chimica Acta, 1035, 96–107. https://doi.org/10.1016/j.aca.2018.07.034Livia Melo Arruda Cunha. (2009). Estudo Fitoquímico e Biológico de Duguetia riparia (Annonaceae)S.Lobão, A. Q. , L. J. C. , E. R. H. J. , M.-S. I. , P. P. A. F. , S. L. V. , O. M. L. B. , J. D. , M. R. (2020). Annonaceae in Flora do Brasil 2020. Jardim Botânico do Rio de Janeiro. : : Http:// Floradobrasil.Jbrj.Gov.Br/Reflora/Floradobrasil/FB110219.Lúcio, A. S. S. C., Almeida, J. R. G. da S., da-Cunha, E. V. L., Tavares, J. F., & Barbosa Filho, J. M. (2015). Alkaloids of the Annonaceae: Occurrence and a Compilation of Their Biological Activities. Alkaloids: Chemistry and Biology, 74, 233–409. https://doi.org/10.1016/bs.alkal.2014.09.002Michopoulos, F., Gika, H., Palachanis, D., Theodoridis, G., & Wilson, I. D. (2015). Solid phase extraction methodology for UPLC-MS based metabolic profiling of urine samples. Electrophoresis, 36(18), 2170–2178. https://doi.org/10.1002/elps.201500101Murillo, J. (2001). Las Annonaceae de Colombia. In Biota Colombiana (Vol. 2, Issue 1).Nothias, L. F., Petras, D., Schmid, R., Dührkop, K., Rainer, J., Sarvepalli, A., Protsyuk, I., Ernst, M., Tsugawa, H., Fleischauer, M., Aicheler, F., Aksenov, A. A., Alka, O., Allard, P. M., Barsch, A., Cachet, X., Caraballo-Rodriguez, A. M., Da Silva, R. R., Dang, T., … Dorrestein, P. C. (2020). Feature-based molecular networking in the GNPS analysis environment. Nature Methods, 17(9), 905–908. https://doi.org/10.1038/s41592-020-0933-6Paul J. M. Maas, L. Y. Th. W. L. W. C. (2003). Duguetia (Annonaceae). Published for Organization for Flora Neotropica by the New York Botanical GardenPaz, W. H. P., De Oliveira, R. N., Heerdt, G., Angolini, C. F. F., S. De Medeiros, L., Silva, V. R., Santos, L. S., Soares, M. B. P., Bezerra, D. P., Morgon, N. H., Almeida, J. R. G. S., Da Silva, F. M. A., Costa, E. V, & Koolen, H. H. F. (2019). Structure-Based Molecular Networking for the Target Discovery of Oxahomoaporphine and 8-Oxohomoaporphine Alkaloids from Duguetia surinamensis. Journal of Natural Products, 82(8), 2220–2228. https://doi.org/10.1021/acs.jnatprod.9b00287Silva, A. F., Rabelo, M. F. R., & Enoque, M. M. (2015). Diversidade de angiospermas e espécies medicinais de uma área de Cerrado. Revista Brasileira de Plantas Medicinais, 17(4), 1016–1030. https://doi.org/10.1590/1983-084X/14_115Tilvi, S., Majik, M. S., & Singh, K. S. (2014). Mass spectrometry for determination of bioactive compounds. In Comprehensive Analytical Chemistry (Vol. 65, pp. 193–218). Elsevier B.V. https://doi.org/10.1016/B978-0-444-63359-0.00008-2Wang, S., Alseekh, S., Fernie, A. R., & Luo, J. (2019). The Structure and Function of Major Plant Metabolite Modifications. In Molecular Plant (Vol. 12, Issue 7, pp. 899–919). Cell Press. https://doi.org/10.1016/j.molp.2019.06.001Wolfender, J. L., Queiroz, E. F., & Hostettmann, K. (2006). The importance of hyphenated techniques in the discovery of new lead compounds from nature. In Expert Opinion on Drug Discovery (Vol. 1, Issue 3, pp. 237–260). https://doi.org/10.1517/17460441.1.3.237Xue, B., Guo, X., Landis, J. B., Sun, M., Tang, C. C., Soltis, P. S., & Soltis, D. E. (2020). Molecular Phylogenetics and Evolution Accelerated diversification correlated with functional traits shapes extant diversity of the early divergent angiosperm family Annonaceae. Molecular Phylogenetics and Evolution, 142(July 2019), 106659. https://doi.org/10.1016/j.ympev.2019.106659Zhang, A., Sun, H., & Wang, X. (2018). Mass spectrometry-driven drug discovery for development of herbal medicine. In Mass Spectrometry Reviews (Vol. 37, Issue 3, pp. 307–320). John Wiley and Sons Inc. https://doi.org/10.1002/mas.21529Zhang, A., Sun, H., Yan, G., & Wang, X. (2017). Recent developments and emerging trends of mass spectrometry for herbal ingredients analysis. In TrAC - Trends in Analytical Chemistry (Vol. 94, pp. 70–76). Elsevier B.V. https://doi.org/10.1016/j.trac.2017.07.007DuguetiaAnnonaceaeAntioxidantesUHPLC-QTof-MS/MSAlcaloidesDuguetiaAnnonaceaeAntioxidantsUHPLC-QTof-MS/MS/MS,AlkaloidsPublicationLICENSElicense.txtlicense.txttext/plain; charset=utf-815543https://repositorio.unicordoba.edu.co/bitstreams/2d491d22-93a1-40c6-88f8-673a2d7606ae/download73a5432e0b76442b22b026844140d683MD52ORIGINAL_Jose_Raul_Padron_Calderon_.pdf_Jose_Raul_Padron_Calderon_.pdfapplication/pdf2230491https://repositorio.unicordoba.edu.co/bitstreams/e929fcc2-2b19-4741-870b-d8a4378fcb25/download9b2bef764375f448a6cb94c223c3f6aaMD53Autorización_Publicación.pdfAutorización_Publicación.pdfapplication/pdf2485029https://repositorio.unicordoba.edu.co/bitstreams/9e61af65-571e-40d0-8eb7-bb8056d732e3/downloade1b611cde46307c2cd32fef368a960d5MD54TEXT_Jose_Raul_Padron_Calderon_.pdf.txt_Jose_Raul_Padron_Calderon_.pdf.txtExtracted texttext/plain101389https://repositorio.unicordoba.edu.co/bitstreams/4f9b6a25-9d74-4d2b-a38f-4ffafcb20aa3/downloadbca2665cb1a845518fb61e422847827eMD55Autorización_Publicación.pdf.txtAutorización_Publicación.pdf.txtExtracted texttext/plain1875https://repositorio.unicordoba.edu.co/bitstreams/3515ec5a-5a52-4ae5-a80d-1be0d40e28d1/downloadd5b4dad4fa551bfa00ffedeb17697cffMD57THUMBNAIL_Jose_Raul_Padron_Calderon_.pdf.jpg_Jose_Raul_Padron_Calderon_.pdf.jpgGenerated Thumbnailimage/jpeg6833https://repositorio.unicordoba.edu.co/bitstreams/5b125446-b819-492b-9e5d-808dd3ff9f7f/download149b6ab207f84b5456a77aea79858f6dMD56Autorización_Publicación.pdf.jpgAutorización_Publicación.pdf.jpgGenerated Thumbnailimage/jpeg14294https://repositorio.unicordoba.edu.co/bitstreams/7ae3fec2-6e63-47c7-8380-45ecd82ea50e/downloadeb0150d01bf04c7d6dc29bb3e77161f2MD58ucordoba/8645oai:repositorio.unicordoba.edu.co:ucordoba/86452024-08-27 03:01:01.428https://creativecommons.org/licenses/by-nc-nd/4.0/Copyright Universidad de Córdoba, 2024embargohttps://repositorio.unicordoba.edu.coRepositorio Universidad de Córdobabdigital@metabiblioteca.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 |