Evaluación de la actividad antiagregante plaquetaria de compuestos derivados de ácido cafeico obtenidos por semisíntesis
ilustraciones
- Autores:
-
Rodriguez Castiblanco, Jessyca Paola
- Tipo de recurso:
- Fecha de publicación:
- 2022
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/83793
- Palabra clave:
- 540 - Química y ciencias afines
Enfermedades cardiovasculares
Productos biológicos
Cardiovascular Diseases
Biological Products
Ácido araquidónico
Ácido cafeico
Antiagregante plaquetario
Derivados de ácido cafeico
Arachidonic acid
Caffeic acid
Platelet antiaggregant
Caffeic acid derivatives
- Rights
- openAccess
- License
- Reconocimiento 4.0 Internacional
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Evaluación de la actividad antiagregante plaquetaria de compuestos derivados de ácido cafeico obtenidos por semisíntesis |
| dc.title.translated.eng.fl_str_mv |
Evaluation of the platelet antiaggregant activity of compounds derived from caffeic acid obtained by semi synthesis |
| title |
Evaluación de la actividad antiagregante plaquetaria de compuestos derivados de ácido cafeico obtenidos por semisíntesis |
| spellingShingle |
Evaluación de la actividad antiagregante plaquetaria de compuestos derivados de ácido cafeico obtenidos por semisíntesis 540 - Química y ciencias afines Enfermedades cardiovasculares Productos biológicos Cardiovascular Diseases Biological Products Ácido araquidónico Ácido cafeico Antiagregante plaquetario Derivados de ácido cafeico Arachidonic acid Caffeic acid Platelet antiaggregant Caffeic acid derivatives |
| title_short |
Evaluación de la actividad antiagregante plaquetaria de compuestos derivados de ácido cafeico obtenidos por semisíntesis |
| title_full |
Evaluación de la actividad antiagregante plaquetaria de compuestos derivados de ácido cafeico obtenidos por semisíntesis |
| title_fullStr |
Evaluación de la actividad antiagregante plaquetaria de compuestos derivados de ácido cafeico obtenidos por semisíntesis |
| title_full_unstemmed |
Evaluación de la actividad antiagregante plaquetaria de compuestos derivados de ácido cafeico obtenidos por semisíntesis |
| title_sort |
Evaluación de la actividad antiagregante plaquetaria de compuestos derivados de ácido cafeico obtenidos por semisíntesis |
| dc.creator.fl_str_mv |
Rodriguez Castiblanco, Jessyca Paola |
| dc.contributor.advisor.none.fl_str_mv |
Guerrero Pabón, Mario Francisco |
| dc.contributor.author.none.fl_str_mv |
Rodriguez Castiblanco, Jessyca Paola |
| dc.contributor.researchgroup.spa.fl_str_mv |
Grupo de Investigaciones en Farmacología Molecular (Farmol) |
| dc.subject.ddc.spa.fl_str_mv |
540 - Química y ciencias afines |
| topic |
540 - Química y ciencias afines Enfermedades cardiovasculares Productos biológicos Cardiovascular Diseases Biological Products Ácido araquidónico Ácido cafeico Antiagregante plaquetario Derivados de ácido cafeico Arachidonic acid Caffeic acid Platelet antiaggregant Caffeic acid derivatives |
| dc.subject.decs.spa.fl_str_mv |
Enfermedades cardiovasculares Productos biológicos |
| dc.subject.decs.eng.fl_str_mv |
Cardiovascular Diseases Biological Products |
| dc.subject.proposal.spa.fl_str_mv |
Ácido araquidónico Ácido cafeico Antiagregante plaquetario Derivados de ácido cafeico |
| dc.subject.proposal.eng.fl_str_mv |
Arachidonic acid Caffeic acid Platelet antiaggregant Caffeic acid derivatives |
| description |
ilustraciones |
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2022 |
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2022-04-25 |
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2023-04-26T19:27:11Z |
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2023-04-26T19:27:11Z |
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Trabajo de grado - Maestría |
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info:eu-repo/semantics/masterThesis |
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https://repositorio.unal.edu.co/handle/unal/83793 |
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Universidad Nacional de Colombia |
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Repositorio Institucional Universidad Nacional de Colombia |
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https://repositorio.unal.edu.co/ |
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https://repositorio.unal.edu.co/handle/unal/83793 https://repositorio.unal.edu.co/ |
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Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia |
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spa |
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Adem, Ş., Eyupoglu, V., Sarfraz, I., Rasul, A., Zahoor, A., Ali, M., & Elfiky, A. (2021). Caffeic acid derivatives (CAFDs) as inhibitors of SARS-CoV-2: CAFDs-based functional foods as a potential alternative approach to combat COVID-19. Phytomedicine, 85, 153310. https://doi.org/10.1016/j.phymed.2020.153310 Alberto, M., Asensio, M., & Sánchez, A. (2018). Fisiología de la función plaquetaria. Hematología(22), 231-237. http://www.sah.org.ar/revista/numeros/vol22/sup/38_Fisiologia_de_la_funcion_pla quetaria.pdf Balachandrán, C., Duraipandiyan, V., Al-Dhabi, N., Balakrishna, K., Kalia, N., Rajput, V., . . . Ignacimuthu, S. (2012). Antimicrobial and Antimycobacterial Activities of Methyl Caffeate Isolated from Solanum torvum Swartz. Fruit. Indian Journal of Microbiology, 54(4), 676-681. https://doi.org/10.1007/s12088-012-0313-8 Bermejo, E. (2017). Plaquetas. Hematología, 10-18. http://www.sah.org.ar/revista/numeros/vol21/extra/06-Vol%2021-extra.pdf Bhullar, K., Lassalle-Claux, G., Touaibia, M., & Rupasinghe, H. (2014). Antihypertensive effect of caffeic acid and its analogs through dual renin–angiotensin–aldosterone system inhibition. European Journal of Pharmacology, 730, 125-132. https://doi.org/10.1016/j.ejphar.2014.02.038 Brass, L. (2003). Thrombin and platelet activation. Chest Journal, 124(3), 18S-25S. https://doi.org/10.1378/chest.124.3_suppl.18s Brass, L., Tomaiuolo, M., & Stalker, T. (2013). Harnessing the platelet signaling network to produce an optimal hemostatic response. Hematology/Oncology Clinics of North America, 27(3), 381-409. https://doi.org/10.1016/J.Hoc.2013.02.002 Buitrago, D. (2012). Estudio de los mecanismos antihipertensivos y antiagregantes plaquetarios de los metabolitos secundarios obtenidos de Solanum tuberosum. [Tesis doctoral]. Bogotá, D. C.: Universidad Nacional de Colombia. Buitrago, D., Puebla, P., & Guerrero, M. (2019). Antiplatelet activity of metabolites isolated from Solanum tuberosum. Latin American Journal of Pharmacy, 38(8), 1575-1581. Buitrago, D., Ramos, G., Rincón, J., & Guerrero, M. (2007). Actividad antiagregante del extracto etanólico de Solanum tuberosum en plaquetas humanas. Vitae, 14(1), 49- 54. http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0121- 40042007000100007 Farndale, R. (2006). Collagen-induced platelet activation. Blood Cells, Molecules, and Diseases, 36(2), 162-165. https://doi.org/10.1016/j.bcmd.2005.12.016 Fitzgerald, G. (1991). Mechanisms of platelet activation: thromboxane A2 as an amplifying signal for other agonists. The American Journal of Cardiology, 68(7), B11–B15. https://doi.org/10.1016/0002-9149(91)90379-y Fontana, P. (2003). Adenosine diphosphate-induced platelet aggregation is associated with P2Y12 gene sequence variations in healthy subjects. Circulation, 108(8), 989-995. https://doi.org/10.1161/01.cir.0000085073.69 Geraldo, R., Sathler, P., Lourenço, A., Saito, M., Cabral, L. R., & Castro, H. (2014). Platelets: still a therapeutical target for haemostatic disorders. International Journal of Molecular Sciences, 15(10), 17901-17919. https://doi.org/10.3390/ijms151017901 González, A, Bizarro P, Rojas M. (2019). El megacariocito: una célula muy original. Rev. Fac. Med. (Méx.) ; 62( 1 ): 6-18. https://doi.org/10.22201/fm.24484865e.2019.62.1.02. Ghoshal, K., & Bhattacharyya, M. (2014). Overview of platelet physiology: its hemostatic and nonhemostatic. Role in Disease Pathogenesis, 1-16. https://doi.org/10.1155/2014/781857 Gresele, P., Born, G., Patrono, C., & Page, C. (2012). Antiplatelet agents. Springer. https://doi.org/10.1007/978-3-642-29423-5 Harrison, P. (2005). Platelet function analysis. Blood Reviews, 19(2), 111–123. https://doi.org/10.1016/j.blre.2004.05.002. Hsiao, G., Lee, J., Lin, K., Shen, C., Fong, T., Chou, D., & Sheu, J. (2007). Characterization of a novel and potent collagen antagonist, caffeic acid phenethyl ester, in human platelets: In vitro and in vivo studies. Cardiovascular Research, 75(4), 782-792. https://doi.org/10.1016/j.cardiores.2007.05.005 Hung, C., Tsai, W., Kuo, L., & Kuo, Y. (2005). Evaluation of caffeic acid amide analogues as anti-platelet aggregation and anti-oxidative agents. Bioorganic & Medicinal Chemistry, 13(5), 131791-131797. https://doi.org/10.1016/j.bmc.2004.11.055 Jantas, D., Chwastek, J., Malarz, J., Stojakowska, A., & Lasoń, W. (2020). Neuroprotective effects of methyl caffeate against hydrogen peroxide-induced cell damage: involvement of caspase 3 and cathepsin D inhibition. Biomolecules, 10(11), 1530. https://doi.org/10.3390/biom10111530 Jeske, W. (2020). Platelet production, structure, and function. Rodak’s Hematology, 136- 153. https://doi.org/10.1016/b978-0-323-53045-3.00019-2 Kinra, M., Arora, D., Mudgal, J., Pai, K., Mallikarjuna, C., & Nampoothiri, M. (2019). Effect of caffeic acid on ischemia-reperfusion-induced acute renal failure in rats. Pharmacology, 103(5-6), 315-319. https://doi.org/10.1159/000497474 Koupenova, M., & Ravid, K. (2018). Biology of platelet purinergic receptors and implications for platelet heterogeneity. Frontiers in Pharmacology, 9. https://doi.org/10.3389/fphar.2018.00037 Kyung, M., Lee, Y., & Yun-Choi, H. (2002). Anti-platelet effect of the constituents isolated from the barks and fruits of Magnolia obovata. Archives of Pharmacal Research, 25(3), 325-328. https://doi.org/10.1007/BF02976634 Lee, D., Kim, H., Cho, H., Bae, J., Yu, Y., & Park, H. (2014). Antiplatelet effects of caffeic acid due to Ca2＋ mobilizationinhibition via cAMP-dependent Inositol-1, 4, 5- Trisphosphate receptor phosphorylation. Journal of Atherosclerosis and Thrombosis, 21(1), 23-37. https://doi.org/10.5551/jat.18994 Lim, H., Kyu, P., Shin, Y. S., Yong, K., & Hyun, K. (2017). Methyl caffeate and some plant constituents inhibit age-related inflammation: effects on senescence-associated secretory phenotype (SASP) formation. Archives of Pharmacal Pharmacal Research, 40(4), 524-535. https://doi.org/10.1007/s12272-017-0909-y Linden, M., Frelinger, A., Barnard, M., Przyklenk, K., Furman, M., & Michelson, A. (2004). Application of flow cytometry to platelet disorders. Seminars in Thrombosis and Hemostasis, 30(5), 501-511. https://doi.org/10.1055/s-2004-835671 Liu, Y. (2012). Patente nº EP2640376A2 Lu, Y., Li, Q., Liu, Y., Sun, K., Fan, J., Wang, C., & Han, J. (2015). Inhibitory effect of caffeic acid on ADP-induced thrombus formation and platelet activation involves mitogenactivated protein kinases. Scientific Reports, 5, 13824. https://doi.org/10.1038/srep13824 Majithia, A., & Bhatt, D. (2019). Novel Antiplatelet Therapies for Atherothrombotic diseases. Arteriosclerosis, Thrombosis, and Vascular Biology, 39, 546–557. https://doi.org/10.1161/ATVBAHA.118.310955 Michelson, A. (2013). Platelets. Academic Press. Ministerio de Salud. (1993). Resolución 8430 del 4 de octubre de 1993. [Por la cual se establecen las normas científicas, técnicas y administrativas para la investigación en salud]. Bogotá, D. C., Colombia. https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/DE/DIJ/RESOL UCION-8430-DE-1993.PDF Monteiro, K., Guimarães, R., Mosquera, L., Rocha, A., Machado, A., Bispo, A., . . . Chagas, M. (2019). Chemical and pharmacological aspects of caffeic acid and its activity in hepatocarcinoma. Frontiers in Oncology, 9, 541. https://doi.org/10.3389/fonc.2019.00541 Monteiro, M., O´Connor, J., & Martínez, M. (2001). La citometría de flujo en el análisis de las plaquetas: (I) aspectos estructurales y funcionales de las plaquetas. Revista de Diagnóstico Biológico, 50(3), 111-136. https://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S0034- 79732001000300002&lng=e Muhammad, N., Ahmad, F., Teoh, S., & Yahaya, M. (2021). Caffeic acid on metabolic syndrome: a review. Molecules, 26(18), 5490. https://doi.org/10.3390/molecules26185490 Murugappan, S. (2006). The role of ADP receptors in platelet function. Frontiers in Bioscience, 11(1), 1977-1986. https://doi.org/10.2741/1939 Offermanns, S. (2006). Activation of platelet function through G protein-coupled receptors. Circulation Research, 99(12), 1293-1304. https://doi.org/10.1161/01.res.0000251742.713 Pyo, M., Lee, Y., & Yun-Choi, H. (2002). Anti-platelet effect of the constituents isolated from the barks and fruits of Magnolia obovata. Archives of Pharmacal Research, 25(3), 325-328. https://doi.org/10.1007/bf0297663 Rajiv, G., Ignacimuthu, S., Paulraj, M., & Sasikumar, P. (2011). Antihyperglycemic activity and antidiabetic effect of methyl caffeate isolated from Solanum torvum Swartz. fruit in streptozotocin induced diabetic rats. European Journal of Pharmacology, 670(2), 623-631. https://doi.org/10.1016/j.ejphar.2011.09.159 Sánchez-Arias, A., Bobadilla-Serrano, M., Dimas-Altamirano, B., Gómez-Ortega, M., & González-González, G. (2016). Enfermedad cardiovascular: primera causa de morbilidad. Revista Mexicana de Cardiología, 27(s3), s98-s102. https://www.medigraphic.com/cgi-bin/new/resumen.cgi?IDARTICULO=66578 Silva, H., & Lopes, N. (2020). Cardiovascular effects of caffeic acid and its derivatives: a comprehensive review. Frontiers in Physiology, 11, 595516. https://doi.org/10.3389/fphys.2020.595516 Silva, T., Oliveira, C., & Borges, F. (2014). Caffeic acid derivatives, analogs and applications: a patent review (2009 – 2013). Expert Opinion on Therapeutic Patents, 24(11), 1257-1270. https://doi.org/10.1517/13543776.2014.959492 Solla, I., Bembibre, L., & Freire, J. (2011). Manejo del Síndrome coronario agudo en Urgencias de Atención Primaria. Cadernos de Atención Primaria, 18(1), 49-55. https://www.agamfec.com/wp/wp-content/uploads/2014/07/18_1_actua_1.pdf Spencer, F., & Becker, R. (1997). Platelets: structure, function, and their fundamental contribution to hemostasis and pathologic thrombosis. In: Becker R.C. (eds). En R. Becker, Textbook of coronary thrombosis and thrombolysis. Developments in cardiovascular medicine. Springer. https://doi.org/10.1007/978-0-585-33754-8_3 Texas Heart Institute. (2020). Enfermedad arterial coronaria. Texas Heart Institute: https://www.texasheart.org/heart-health/heartinformationcenter/topics/enfermedad-arterial-coronaria/ Tyszka-Czochara, M., Bukowska-Strakova, K., Kocemba-Pilarczyk, K., & Majka, M. (2018). Caffeic acid targets AMPK signaling and regulates tricarboxylic acid cycle anaplerosis while metformin downregulates HIF-1α-Induced glycolytic enzymes in human cervical squamous cell carcinoma lines. Nutrients, 10(7), 841. https://doi.org/10.3390/nu10070841 Van der Meijden, P., & Heemskerk, J. (2019). Platelet biology and functions: new concepts and clinical perspectives. Nature Reviews Cardiology, 16, 166-179. https://doi.org/10.1038/s41569-018-0110-0 Varga-Szabo, D., Pleines, I., & Nieswandt, B. (2008). Cell adhesion mechanisms in platelets. Arteriosclerosis, Thrombosis, and Vascular Biology, 28(3), 403-412. https://doi.org/10.1161/atvbaha.107.150474 Veeren, B., Bringart, M., Turpin, C., Rondeau, P., Planesse, C., Ait-Arsa, I., & Bascands, J. (2021). Caffeic acid, one of the major phenolic acids of the medicinal plant antirhea borbonica, reduces renal tubulointerstitial fibrosis. Biomedicines, 9(4), 358. https://doi.org/10.3390/biomedicines9040358 Wang, A., Leible, M., Lin, J., Weiss, J., & Zhong, Q. (2020). Caffeic acid phenethyl ester loaded in skim milk microcapsules: physicochemical properties and enhanced in vitro bioaccessibility and bioactivity against colon cancer cells. Journal of Agricultural and Food Chemistry, 68(50), 14978-14987. https://doi.org/10.1021/acs.jafc.0c05143 |
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Universidad Nacional de Colombia |
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Bogotá - Ciencias - Maestría en Ciencias - Farmacología |
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Facultad de Ciencias |
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Bogotá, Colombia |
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Universidad Nacional de Colombia - Sede Bogotá |
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Reconocimiento 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Guerrero Pabón, Mario Franciscoab5ee54c43da4b4b657356c0e0296aa6Rodriguez Castiblanco, Jessyca Paoladbf875292c0affe6192703a02f8541deGrupo de Investigaciones en Farmacología Molecular (Farmol)2023-04-26T19:27:11Z2023-04-26T19:27:11Z2022-04-25https://repositorio.unal.edu.co/handle/unal/83793Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustracionesResumen Evaluación de la actividad antiagregante plaquetaria de compuestos derivados de ácido cafeico obtenidos por semisíntesis Las enfermedades cardiovasculares siguen siendo la principal causa de mortalidad en el mundo, por ello son de gran interés en salud pública. El desarrollo de nuevas terapias antiplaquetarias presentes en el reino vegetal dirigidas a receptores y vías de señalización claves en el mantenimiento de la eficacia antiplaquetaria preservando la hemostasia, es un enorme reto para la investigación. El objetivo de este trabajo fue evaluar la actividad antiagregante plaquetaria de compuestos derivados de ácido cafeico obtenidos por semisíntesis. Metodología. Para la evaluación del efecto antiagregante se empleó la técnica de agregometría de transmisión de luz (LTA), con 21 ml de sangre total de voluntarios sanos, siguiendo dos fases: La fase 1, para efectuar un tamizado de la actividad antiagregante de todos los compuestos y la fase 2, para efectuar curvas concentración – respuesta de 3 de los compuestos de mayor actividad detectados en la fase 1. Resultados. En la fase I todos los compuestos, ensayados a la concentración inicial de tamizado de 200 µg/ml, mostraron efectos antiagregantes marcados frente a los inductores de la agregación plaquetaria ácido araquidónico (AA, 500 µg/ml) y epinefrina (300 µM), con porcentajes de agregación inferior al 34%, mientras se observó una respuesta antiagregante baja en todos los casos frente a ADP (20 uM), con porcentajes de agregación superior a 60% y variable, frente a colágeno (10 ug/ml), con porcentajes entre el 25 y 65%, según el compuesto evaluado. En la fase 2, se probaron los compuestos de mayor actividad de la fase 1: 3-(3-hidroxifenil) acrilato de etilo, cafeato de butilo y metil cinamato frente a AA, de los cuales, 3-(3 hidroxifenil) acrilato de etilo arrojó un perfil concentración – respuesta, con una concentración efectiva 50 (1,22x10 -7 M) similar a la del compuesto fuente, ácido cafeico. Conclusión: Modificaciones estructurales de ácido cafeico llevan a la obtención de compuestos que mantienen una actividad variable de tipo antiagregante plaquetaria, vinculada con la ruta metabólica del ácido araquidónico, resultando de particular interés el compuesto 3-(3-hidroxifenil) acrilato de etilo, cuya potencia antiagregante es comparable a la obtenida con el compuesto fuente, ácido cafeico, lo que le genera interés como compuesto semisintético con potenciales efectos antiagregantes plaquetarios. Texto tomado de la fuente)Evaluation of the platelet antiaggregant activity of compounds derived from caffeic acid obtained by semi synthesis Cardiovascular diseases continue to be the main cause of mortality in the world, which is why they are of great interest in public health. The development of new antiplatelet therapies presents in the plant kingdom targeting additional receptors and signaling pathways, with a focus on maintaining antiplatelet efficacy while preserving hemostasis, is an enormous research challenge. The objective of this work was to evaluate the antiplatelet activity of compounds derived from caffeic acid obtained by semisynthesis. Methodology for the evaluation of the antiplatelet effect, two phases were followed -using the light transmission aggregometric technique (LTA), with 21 ml of whole blood from healthy volunteers- phase I, to screen the antiplatelet activity of all the compounds phase II, to make concentration-response curves of 3 of the most active compounds detected in phase 1. Next, all the compounds in the phase 1, tested at the initial screening concentration of 200 μg/ml, showed marked antiaggregation effects against the platelet aggregation inducers (PA), arachidonic acid (AA,500 μg/ml) and epinephrine (EPI) (300 μM), with aggregation percentages below 34 %; while a low antiplatelet response was observed in all cases against ADP (20 uM), with aggregation percentage above 60 % and a variable against collagen (COL), between 25 % - 65 %, depending on the compound evaluated. An effect that was confirmed in phase II, with the most active compounds: 3-(3-hydroxyphenyl) ethyl acrylate, butyl caffeate and methyl cinnamate, of which, 3-(3-hydroxyphenyl) ethyl acrylate gave an effective concentration 50 (1,22 x 10-7M) similar to that of the source compound, caffeic acid. Finally, the structural modifications of caffeic acid lead to the obtaining of compounds that maintain a variable activity of platelet antiaggregant type, linked to the metabolic pathway of arachidonic acid, being of particular interest the compound 3-(3- hydroxyphenyl) ethyl acrylate whose potency antiaggregant is comparable to that obtained with the source compound, caffeic acid, which generates interest as a semi-synthetic compound with potential platelet antiaggregant effects.MaestríaMagíster en Ciencia - Farmacologíafarmacología experimental basica75 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - FarmacologíaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá540 - Química y ciencias afinesEnfermedades cardiovascularesProductos biológicosCardiovascular DiseasesBiological ProductsÁcido araquidónicoÁcido cafeicoAntiagregante plaquetarioDerivados de ácido cafeicoArachidonic acidCaffeic acidPlatelet antiaggregantCaffeic acid derivativesEvaluación de la actividad antiagregante plaquetaria de compuestos derivados de ácido cafeico obtenidos por semisíntesisEvaluation of the platelet antiaggregant activity of compounds derived from caffeic acid obtained by semi synthesisTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMAdem, Ş., Eyupoglu, V., Sarfraz, I., Rasul, A., Zahoor, A., Ali, M., & Elfiky, A. 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Journal of Agricultural and Food Chemistry, 68(50), 14978-14987. https://doi.org/10.1021/acs.jafc.0c05143Evaluación de la actividad antiagregante plaquetaria de compuestos derivados de ácido cafeico obtenidos por semisíntesisEstudiantesLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/83793/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL10693042602022.pdf10693042602022.pdfMaestría en Ciencias - Farmacologíaapplication/pdf1411429https://repositorio.unal.edu.co/bitstream/unal/83793/2/10693042602022.pdf5c42433a7baca173a871c7a2291731a9MD52THUMBNAIL10693042602022.pdf.jpg10693042602022.pdf.jpgGenerated Thumbnailimage/jpeg5041https://repositorio.unal.edu.co/bitstream/unal/83793/3/10693042602022.pdf.jpg2f73bb27fbfa9c259632f1bf62b8846aMD53unal/83793oai:repositorio.unal.edu.co:unal/837932024-08-05 23:10:26.44Repositorio Institucional Universidad Nacional de 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