Determinación del mecanismo de acción de diferentes AINEs a partir de su potencial inhibitorio sobre COX y los receptores de prostaglandina

El uso extendido de los AINEs ha conllevado al planteamiento de preocupaciones sobre sus efectos secundarios, especialmente cuando se emplean sin supervisión médica. A nivel molecular, estos fármacos inhiben la ciclooxigenasa (COX), enzimas que desempeñan un papel crucial en la producción de prostag...

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Autores:
Farías Arriaga, Delfina Pilar
Tipo de recurso:
Trabajo de grado de pregrado
Fecha de publicación:
2024
Institución:
Universidad ICESI
Repositorio:
Repositorio ICESI
Idioma:
spa
OAI Identifier:
oai:repository.icesi.edu.co:10906/130358
Acceso en línea:
https://hdl.handle.net/10906/130358
https://biblioteca2.icesi.edu.co/cgi-olib/?oid=365044
Palabra clave:
AINEs
COX
Prostaglandinas
Trabajos de grado de Química Farmacéutica
NSAIDs
COX
Prostaglandins
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-nd/4.0/
id ICESI2_e3fff2dcc9e21a186d3b866e2bf483db
oai_identifier_str oai:repository.icesi.edu.co:10906/130358
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network_name_str Repositorio ICESI
repository_id_str
dc.title.none.fl_str_mv Determinación del mecanismo de acción de diferentes AINEs a partir de su potencial inhibitorio sobre COX y los receptores de prostaglandina
title Determinación del mecanismo de acción de diferentes AINEs a partir de su potencial inhibitorio sobre COX y los receptores de prostaglandina
spellingShingle Determinación del mecanismo de acción de diferentes AINEs a partir de su potencial inhibitorio sobre COX y los receptores de prostaglandina
AINEs
COX
Prostaglandinas
Trabajos de grado de Química Farmacéutica
NSAIDs
COX
Prostaglandins
title_short Determinación del mecanismo de acción de diferentes AINEs a partir de su potencial inhibitorio sobre COX y los receptores de prostaglandina
title_full Determinación del mecanismo de acción de diferentes AINEs a partir de su potencial inhibitorio sobre COX y los receptores de prostaglandina
title_fullStr Determinación del mecanismo de acción de diferentes AINEs a partir de su potencial inhibitorio sobre COX y los receptores de prostaglandina
title_full_unstemmed Determinación del mecanismo de acción de diferentes AINEs a partir de su potencial inhibitorio sobre COX y los receptores de prostaglandina
title_sort Determinación del mecanismo de acción de diferentes AINEs a partir de su potencial inhibitorio sobre COX y los receptores de prostaglandina
dc.creator.fl_str_mv Farías Arriaga, Delfina Pilar
dc.contributor.advisor.none.fl_str_mv Rodríguez, Laura María
dc.contributor.author.none.fl_str_mv Farías Arriaga, Delfina Pilar
dc.subject.proposal.spa.fl_str_mv AINEs
COX
Prostaglandinas
Trabajos de grado de Química Farmacéutica
topic AINEs
COX
Prostaglandinas
Trabajos de grado de Química Farmacéutica
NSAIDs
COX
Prostaglandins
dc.subject.proposal.eng.fl_str_mv NSAIDs
COX
Prostaglandins
description El uso extendido de los AINEs ha conllevado al planteamiento de preocupaciones sobre sus efectos secundarios, especialmente cuando se emplean sin supervisión médica. A nivel molecular, estos fármacos inhiben la ciclooxigenasa (COX), enzimas que desempeñan un papel crucial en la producción de prostaglandinas. Los AINEs tienen diferentes blancos de acción y con afinidades diversas, volviéndose más específicas frente a una isoforma respecto a la otra. No obstante, se desconoce cómo estos medicamentos afectan específicamente los receptores de prostaglandinas y el mecanismo exacto de su efecto inhibitorio sobre las ciclooxigenasas, lo que justifica la necesidad de investigar a profundidad para elucidar su acción. Por este motivo, el presente proyecto tiene como finalidad contribuir a la investigación científica en describir el mecanismo de acción de AINEs seleccionados con base en su grado inhibitorio sobre ciclooxigenasa y la expresión de los receptores de prostaglandina. Para ello, se evaluó el efecto inhibitorio de seis AINEs sobre la ciclooxigenasa en la producción de PGF2α mediante ELISA competitivo y su efecto en la expresión de los receptores EP1, EP2, EP3 y EP4 en la línea celular HGC-27. Con ello, se confirmó la selectividad hacia COX-2 por el etoricoxib y celecoxib, se constató una alta inhibición del acetaminofén hacia COX y el ibuprofeno demostró una tendencia no selectiva frente a las ciclooxigenasas. Además, el meloxicam y el diclofenaco evidenciaron un efecto sobre los receptores de prostaglandina, siendo más equilibrado el efecto del diclofenaco. Asimismo, este estudio permitió establecer las concentraciones inhibitorias efectivas de dichos AINEs y su efecto sobre COX y receptores PGE2, proporcionando una base para optimizar su uso y conocer sus tendencias moleculares.
publishDate 2024
dc.date.issued.none.fl_str_mv 2024-12-12
dc.date.accessioned.none.fl_str_mv 2025-06-13T20:11:56Z
dc.date.available.none.fl_str_mv 2025-06-13T20:11:56Z
dc.type.none.fl_str_mv bachelor thesis
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_7a1f
dc.type.local.none.fl_str_mv Trabajo de grado
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dc.relation.references.spa.fl_str_mv 1. Ghlichloo, I. & Gerriets, V. Nonsteroidal Anti - inflammatory Drugs (NSAIDs). PubMed https://www.ncbi.nlm.nih.gov/books/NBK547742/ (2023).
2. Takeuchi, K., Amagase, K. Roles of Cyclooxygenase, Prostaglandin E2 and EP Receptors in Mucosal Protection and Ulcer Healing in the Gastrointestinal Tract. Curr Pharm Des. PMID: 29956615 (2018). doi: 10.2174/1381612824666180629111227.
3. Bindu S, Mazumder S, Bandyopadhyay U. Non - steroidal anti - inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol. PMID: 32653589; PMCID: PMC7347500. (2020). doi: 10.1016/j.bcp.2020.114147.
4. Zhang P, Luo HS, Li M, Tan SY. Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX - 2. Onco Targets Ther. Apr 16;8:845 - 54. (2015). doi: 10.2147/OTT.S81041
5. Zhang, B. et al. PGD2/PTGDR2 signalling restricts the self - renewal and tumorigenesis of gastric cancer. Stem Cells 36, 990 – 1003. (2018).
6. Mazumder, S., Bindu, S., Debsharma, S., Bandyopadhyay, U. Induction of mitochondrial toxicity by non - steroidal anti - inflammatory drugs (NSAIDs): The ultimate trade - off governing the therapeutic merits and demerits of these wonder drugs. Biochem Pharmacol . PMID: 38750902. (2024). doi: 10.1016/j.bcp.2024.116283.
7. Dvorakova, M., Langhansova, L., Temml, V., Pavicic, A., Vanek, T. & Landa, P. Synthesis, Inhibitory Activity, and In Silico Modeling of Selective COX - 1 Inhibitors with a Quinazoline Core. ACS Medicinal Chemistry Letters 12 (4), 610 - 616. (2021). DOI: 10.1021/acsmedchemlett.1c00004.
8. Minhajul, A., Ashish, S., Noopur, S., Riaz, A., Khan, S., Almahmoud, A., Hamdoon, A. Design, classification, and adverse effects of NSAIDs: A review on recent advancements, Bioorganic & Medicinal Chemistry, Volume 112, 117899, ISSN 0968 - 0896. (2024). https://doi.org/10.1016/j.bmc.2024.117899
9. Ribeiro, H., Rodrigues, I., Napoleão, L., Lira, L., Marques, D., Veríssimo, M., Andrade, J.P., Dourado, M. Non - steroidal anti - inflammatory drugs (NSAIDs), pain and aging: Adjusting prescription to patient features, Biomedicine & Pharmacotherapy, Volume 150 , 112958, ISSN 0753 - 3322. (2022). https://doi.org/10.1016/j.biopha.2022.112958 .
10. Fokunang, C. Overview of non - steroidal anti - inflammatory drugs (nsaids) in resource limited countries. MOJ Toxicology 4. (2018).
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12. Grosjean, N., Yee, E.F., Kumaran, D. et al. A hemoprotein with a zinc - mirror heme site ties heme availability to carbon metabolism in cyanobacteria. Nat Commun 15, 3167 (2024). https://doi.org/10.1038/s41467 - 024 - 47486 - z
13. Wang, B., Wu, L., Chen, J. et al. Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets. Sig Transduct Target Ther 6, 94. (2021). https://doi.org/10.1038/s41392 - 020 - 00443 - w
14. Zhang, Y., Liu, Y., Sun, J., Zhang, W., Guo, Z., Ma, Q. Arachidonic acid metabolism in health and disease. MedComm. PMID: 37746665; PMCID: PMC10511835. (2023). doi: 10.1002/mco2.363.
15. Tallima, H. Clarification of Arachidonic Acid Metabolic Pathway Intricacies ACS Omega (24), 15559 - 15563. DOI: 10.1021/acsomega.1c01952. (2021).
16. Li, X - J., Suo, P., Wang, Y - N., Zou, L., Nie, X - L., Zhao, Y - Y., Miao H. Arachidonic acid metabolism as a therapeutic target in AKI - toCKD transition. Front. Pharmacol. 15:1365802 (2024). doi: 10.3389/fphar.2024.1365802.
17. Alfaro RA, Davis DD. Diclofenac. Treasure Island (FL): StatPearls Publishing. (2023). https://www.ncbi.nlm.nih.gov/books/NBK557879/
18. DICLOFENAC: AN UPDATE ON ITS MECHANISM OF ACTION AND SAFETY PROFILE. Journal of Population Therapeutics and Clinical Pharmacology , 30 (2), 830 - 833. (2023). https://doi.org/10.53555/jptcp.v30i2.4862
19. García Aguirre L, Bohorquez Nassar C, Ruiz Olmedo I, Dennie L, Medina Nolasco AG. Bioequivalence Evaluation of Two Oral Formulations of Acetaminophen in Healthy Subjects: Results From a Randomized, Single - Blind, Crossover Study. Clin Pharmacol Drug Dev. 20 19 Jan;8(1):9 - 15. doi: 10.1002/cpdd.469. Epub 2018 May 11. PMID: 29749718 ; PMCID: PMC6667897.
20. Geith, S., Renner, B., Rabe, C. et al. Ibuprofen plasma concentration profile in deliberate ibuprofen overdose with circulatory depression treated with therapeutic plasma exchange: a case report. BMC Pharmacol Toxicol 18 , 81 (2017). https://doi.org/10.1186/s40360 - 017 - 0187 - 9
21. CLINICAL PHARMACOLOGY AND BIOPHARMACEUTICS REVIEW(S) . CENTER FOR DRUG EVALUATION AND RESEARCH (FDA). (2017). https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/125545Orig1s000 ClinPharmR.pdf
22. Hasan, Syed Muhammad Farid & Ahmad, Tasneem & Talib, Nasira & Hasan, Fouzia. Pharmacokinetics of diclofenac sodium in normal man. Pakistan journal of pharmaceutical sciences. (2005).
23. Harikrishnan, N. et al . ‘Pharmacokinetics and bioequivalence of generic etoricoxib in Healthy Volunteers’, Generics and Biosimilars Initiative Journal , 10(3), pp. 113 – 118. (2021). doi:10.5639/gabij.2021.1003.013.
24. Chang WK et al. Bioequivalence Evaluation of two Formulations of Celecoxib 200mg Capsules in Healthy volunteers by using a validated LC/MS/MS method. Int J Bioanal Methods Bioequival Stud, 2(2), 34 - 40. (2015). doi: http://dx.doi.org/10.19070/2470 - 4490 - 150004
25. Patrignani, P., Panara, M.R, Greco, A., Fusco, O., Natoli, C., Iacobelli S, et al. Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. J Pharmacol Exp Ther. 1994;271(3): 1705 – 12
26. Shin VY, Liu MX, Siu JM, Kwong A, Chu KM. Inhibition of EP2 receptor suppresses tumor growth and chemoresistance of gastric cancer. Am J Cancer Res. (2022). 15;12(10):4680 - 4692. PMID: 36381319; PMCID: PMC9641405.
27. Matheny, R.W. Jr, Kolb, A.L., Geddis, A.V., Roberts, B.M. Celecoxib impairs primary human myoblast proliferation and differentiation independent of cyclooxygenase 2 inhibition. Physiol Rep.;10(21):e15481. (2022). doi: 10.14814/phy2.15481. PMID: 36325583; P MCID: PMC9630763.
28. Riaposova, L., Kim, S.H., Hanyaloglu, A.C., Sykes, L., MacIntyre D.A., Bennett, P.R., Terzidou, V. Prostaglandin F2a requires activation of calcium - dependent signalling to trigger inflammation in human myometrium. Front. Endocrinol. (2023). 14:1150125. doi : 10.3389/fendo.2023.1150125
29. Bancos, S. B., Phipps, R. Ibuprofen and other widely used non - steroidal anti - inflammatory drugs inhibit antibody production in human cells. Cellular immunology. 258. 18 - 28. (2009). 10.1016/j.cellimm.2009.03.007.
30. Vleeshouwers, W., Van den Dries, K., de Keijzer, S., Joosten, B., Lidke, D.S., Cambi, A. Characterization of the Signaling Modalities of Prostaglandin E2 Receptors EP2 and EP4 Reveals Crosstalk and a Role for Microtubules. Front. Immunol. 11:613286. (2021) . doi: 10.3389/fimmu.2020.613286
31. Ayoub, S. S. Paracetamol (acetaminophen): A familiar drug with an unexplained mechanism of action. Temperature , 8 (4), 351 – 371. (2021). https://doi.org/10.1080/23328940.2021.1886392
32. Ayoub, S.S., Flower R.J. Loss of hypothermic and anti - pyretic action of paracetamol in cyclooxygenase - 1 knockout mice is indicative of inhibition of cyclooxygenase - 1 variant enzymes. Eur J Pharmacol . (2019); 861:172609
33. Bashir, S., Elegunde, B., Morgan, W.A. Inhibition of lipolysis: a novel explanation for the hypothermic actions of acetaminophen in non - febrile rodents. Biochem Pharmacol . (2020); 172:113774. https://doi.org/10.1016/j.bcp.2019.113774
34. Ohashi, N., Kohno, T. Analgesic effect of acetaminophen: a review of known and novel mechanisms of action. Front Pharmacol . (2020); 11. https://doi.org/10.3389/fphar.2020.580289
35. Regueras, E., Velázquez, I., Torres, L.M. Actualización en farmacología de los antiinflamatorios no esteroideos: actualización. Revista de la Sociedad Española Multidisciplinar del dolor (Journal of the Multidisciplinary Spanish Pain Society). DOI: 10.2098 6/mpj.2023.1059/2023. (2023).
36. Dong X, Li R, Xiu P, Dong X, Xu Z, Zhai B, et al. Meloxicam Executes Its Antitumor Effects against Hepatocellular Carcinoma in COX - 2 - Dependent and - Independent Pathways. PLoS ONE 9(3): e92864. (2014). https://doi.org/10.1371/journal.pone.0092864
37. Atzeni, F., Masala, I.F. & Sarzi - Puttini, P. A Review of Chronic Musculoskeletal Pain: Central and Peripheral Effects of Diclofenac. Pain Ther 7 , 163 – 177 (2018). https://doi.org/10.1007/s40122 - 018 - 0100 - 2
38. Santiso, A., Heinemann, A., Kargl, J. PGE2 and Its Receptors in the Tumor Microenvironment. Pharmacological Reviews, 76 (3) 388 - 413. (2024). DOI: https://doi.org/10.1124/pharmrev.123.000901
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43. Gomez - Valenzuela, F., Escobar, E., Perez - Tomas, R., Montecinos, V. P. The Inflammatory Profile of the Tumor Microenvironment, Orchestrated by Cyclooxygenase - 2, Promotes Epithelial - Mesenchymal Transition, Front. Oncol. , 11 , 686792, (2021).
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45. Pawlukianiec, C., Gryciuk, M. E., Mil, K. M., Żendzian - Piotrowska, M., Zalewska, A., & Maciejczyk, M. A New Insight into Meloxicam: Assessment of Antioxidant and Anti - Glycating Activity in In Vitro Studies. Pharmaceuticals , 13 (9), 240. (2020). https://doi.org/10.3390/ph13090240
46. K. Cao, Y. Lyu, J. Chen, C. He, X. Lyu, Y. Zhang, L. Chen, Y. Jiang, J. Xiang, B. Liu and C. Wu, Prognostic Implication of Plasma Metabolites in Gastric Cancer, Int. J. Mol. Sci. , 24 (16), 12774, (2023).
47. Kim J. Are nonsteroidal anti - inflammatory drugs safe for the kidney in ankylosing spondylitis?. J Rheum Dis 2023;30:139 - 140. https://doi.org/10.4078/jrd.2023.0033
48. Wautier, J. - L., & Wautier, M. - P. (2023). Pro - and Anti - Inflammatory Prostaglandins and Cytokines in Humans: A Mini Review . International Journal of Molecular Sciences , 24 (11), 9647. https://doi.org/10.3390/ijms24119647
49. Noori M, Yadegar A, Zali MR. 2020. A complex scenario of nonsteroidal antiinflammatory drugs induced prostaglandin E2 production and gut microbiota alteration in Clostridium difficile - infected mice. mBio 11:e02596 - 19. https://doi.org/10.1128/mBio .02596 - 19 .
50. Geurts, F., Chaker, L., van der Burgh, A. C., Cronin - Fenton, D., Fenton, R. A., & Hoorn, E. J. (2024). Urinary Prostaglandin E2 Excretion and the Risk of Cardiovascular and Kidney Disease. Journal of the American Heart Association, 13(4), Article e032835. https://doi.org/10.1161/JAHA.123.032835
51. Ogino, K., Hatanaka, K., Kawamura, M., Ohno, T., & Harada, Y. Meloxicam Inhibits Prostaglandin E2 Generation via Cyclooxygenase 2 in the Inflammatory Site but Not That via Cyclooxygenase 1 in the Stomach. Pharmacology, 61(4), 244 – 250. (2000). doi:10.1159/000028408
52. Taylor S, Gruen M, KuKanich K, et al. 2024 ISFM and AAFP consensus guidelines on the long - term use of NSAIDs in cats. Journal of Feline Medicine and Surgery. 2024;26(4). doi:10.1177/1098612X241241951
53. Jang, Y., Kim, M. & Hwang, S.W. Molecular mechanisms underlying the actions of arachidonic acid - derived prostaglandins on peripheral nociception. J Neuroinflammation 17, 30 (2020). https://doi.org/10.1186/s12974 - 020 - 1703 - 1
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spelling Rodríguez, Laura MaríaFarías Arriaga, Delfina PilarCali de Lat: 03 24 00 N degrees minutes Lat: 3.4000 decimal degrees Long: 076 30 00 W degrees minutes Long: -76.5000 decimal degrees.2025-06-13T20:11:56Z2025-06-13T20:11:56Z2024-12-12https://hdl.handle.net/10906/130358https://biblioteca2.icesi.edu.co/cgi-olib/?oid=365044instname:Universidad Icesireponame:Biblioteca Digitalrepourl:https://repository.icesi.edu.co/El uso extendido de los AINEs ha conllevado al planteamiento de preocupaciones sobre sus efectos secundarios, especialmente cuando se emplean sin supervisión médica. A nivel molecular, estos fármacos inhiben la ciclooxigenasa (COX), enzimas que desempeñan un papel crucial en la producción de prostaglandinas. Los AINEs tienen diferentes blancos de acción y con afinidades diversas, volviéndose más específicas frente a una isoforma respecto a la otra. No obstante, se desconoce cómo estos medicamentos afectan específicamente los receptores de prostaglandinas y el mecanismo exacto de su efecto inhibitorio sobre las ciclooxigenasas, lo que justifica la necesidad de investigar a profundidad para elucidar su acción. Por este motivo, el presente proyecto tiene como finalidad contribuir a la investigación científica en describir el mecanismo de acción de AINEs seleccionados con base en su grado inhibitorio sobre ciclooxigenasa y la expresión de los receptores de prostaglandina. Para ello, se evaluó el efecto inhibitorio de seis AINEs sobre la ciclooxigenasa en la producción de PGF2α mediante ELISA competitivo y su efecto en la expresión de los receptores EP1, EP2, EP3 y EP4 en la línea celular HGC-27. Con ello, se confirmó la selectividad hacia COX-2 por el etoricoxib y celecoxib, se constató una alta inhibición del acetaminofén hacia COX y el ibuprofeno demostró una tendencia no selectiva frente a las ciclooxigenasas. Además, el meloxicam y el diclofenaco evidenciaron un efecto sobre los receptores de prostaglandina, siendo más equilibrado el efecto del diclofenaco. Asimismo, este estudio permitió establecer las concentraciones inhibitorias efectivas de dichos AINEs y su efecto sobre COX y receptores PGE2, proporcionando una base para optimizar su uso y conocer sus tendencias moleculares.The widespread use of NSAIDs has led to concerns about their side effects, especially when used without medical supervision. At the molecular level, these drugs inhibit cyclooxygenase (COX), enzymes that play a crucial role in the production of prostaglandins. NSAIDs have different targets and varying affinities, becoming more specific for one isoform compared to the other. However, it is unknown how these drugs specifically affect prostaglandin receptors and the exact mechanism of their inhibitory effect on cyclooxygenases, which justifies the need for in-depth research to elucidate their action. For this reason, the aim of this project is to contribute to scientific research by describing the mechanism of action of selected NSAIDs based on their inhibitory effect on cyclooxygenase and the expression of prostaglandin receptors. To this end, the inhibitory effect of six NSAIDs on cyclooxygenase in PGF2α production was evaluated using competitive ELISA and their effect on the expression of EP1, EP2, EP3, and EP4 receptors in the HGC-27 cell line. This confirmed the selectivity towards COX-2 by etoricoxib and celecoxib, high inhibition of acetaminophen towards COX was observed, and ibuprofen showed a non-selective tendency towards cyclooxygenases. Furthermore, meloxicam and diclofenac showed an effect on prostaglandin receptors, with the effect of diclofenac being more balanced. Likewise, this study allowed the establishment of the effective inhibitory concentrations of these NSAIDs and their effect on COX and PGE2 receptors, providing a basis for optimizing their use and understanding their molecular trends.1. Resumen ejecutivo -- 2. Introducción -- 2.1 Clasificación de los AINEs -- 2.1.1 Clasificación basada en su estructura química -- 2.1.2 Clasificación basada en su interacción con COX y selectividad -- 2.1.3 Clasificación de los AINEs según la vida media plasmática (t½) y parámetros farmacocinéticos -- 5. Conclusiones -- 6. Agradecimientos -- Referencias Bibliográficas -- Anexos -- Anexo 1. Resultados cuantificación relativa por qPCR bajo tratamiento con Meloxicam y Diclofenaco -- Anexo 2. Configuración placa ELISA competitiva -- Anexo 3. Volumen de reactivo por pozo de reacción en placa ELISA competitivaTrabajo de Grado para obtener el título del Programa de Química FarmacéuticaProfesional35 páginasDigitalapplication/pdfspaUniversidad IcesiBarberi de Ingeniería, Diseño y Ciencias AplicadasQuímica FarmacéuticaSantiago de caliEL AUTOR, expresa que la obra objeto de la presente autorización es original y la elaboró sin quebrantar ni suplantar los derechos de autor de terceros, y de tal forma, la obra es de su exclusiva autoría y tiene la titularidad sobre éste. PARÁGRAFO: en caso de queja o acción por parte de un tercero referente a los derechos de autor sobre el artículo, folleto o libro en cuestión, EL AUTOR, asumirá la responsabilidad total, y saldrá en defensa de los derechos aquí autorizados; para todos los efectos, la Universidad Icesi actúa como un tercero de buena fe. Esta autorización, permite a la Universidad Icesi, de forma indefinida, para que en los términos establecidos en la Ley 23 de 1982, la Ley 44 de 1993, leyes y jurisprudencia vigente al respecto, haga publicación de este con fines educativos Todo persona que consulte ya sea la biblioteca o en medio electróico podrá copiar apartes del texto citando siempre la fuentes, es decir el título del trabajo y el autohttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://purl.org/coar/access_right/c_abf2Determinación del mecanismo de acción de diferentes AINEs a partir de su potencial inhibitorio sobre COX y los receptores de prostaglandinabachelor thesishttp://purl.org/coar/resource_type/c_7a1fTrabajo de gradoinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/bachelorThesisTodo PúblicoAINEsCOXProstaglandinasTrabajos de grado de Química FarmacéuticaNSAIDsCOXProstaglandins1. 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J Neuroinflammation 17, 30 (2020). https://doi.org/10.1186/s12974 - 020 - 1703 - 1ORIGINALTG04025.pdfTG04025.pdfapplication/pdf913073https://repository.icesi.edu.co/bitstreams/78f85e6a-f7fa-4a39-878c-7b1e949e05ec/downloadd0538bd1a0ea6387a950cb7269f79304MD51LICENSElicense.txtlicense.txttext/plain1748https://repository.icesi.edu.co/bitstreams/282e72f8-bea9-40fb-b2f2-76739a016a4c/downloadbb9bdc0b3349e4284e09149f943790b4MD52CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8899https://repository.icesi.edu.co/bitstreams/c62d8b8f-7622-41af-b06e-f2e7a966f455/download3b6ce8e9e36c89875e8cf39962fe8920MD53THUMBNAILTG04025.pdf.jpgTG04025.pdf.jpgIM Thumbnailimage/jpeg2963https://repository.icesi.edu.co/bitstreams/decc066f-c549-4a3b-80cd-f3447b176a3f/download766c3aa28c5d55342533b3d5653a70dfMD5410906/130358oai:repository.icesi.edu.co:10906/1303582025-06-20 08:52:55.258http://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internationalopen.accesshttps://repository.icesi.edu.coBiblioteca Digital - Universidad Icesiadquisicion-bib@listas.icesi.edu.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