Síntesis de un nuevo análogo inhibidor de farnesil pirofosfato sintasa para el tratamiento de la osteoporosis por medio de cribado virtual basado en ligando y estructura

La osteoporosis, una enfermedad de gran relevancia global, afecta a muchas personas y disminuye su calidad de vida. El tratamiento habitual incluye bifosfonatos, utilizados para reducir la regeneración ósea, pero su uso prolongado puede generar efectos adversos debido a la bioacumulación. Este estud...

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Autores:
Quiroga Sarmiento, Santiago
Tipo de recurso:
https://purl.org/coar/resource_type/c_7a1f
Fecha de publicación:
2025
Institución:
Universidad El Bosque
Repositorio:
Repositorio U. El Bosque
Idioma:
spa
OAI Identifier:
oai:repositorio.unbosque.edu.co:20.500.12495/14348
Acceso en línea:
https://hdl.handle.net/20.500.12495/14348
Palabra clave:
In silico
Bifosfonato
Alendronato de sodio
615.19
In silico
Bisphosphonate
Alendronate of sodium
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License
Attribution-NonCommercial-ShareAlike 4.0 International
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oai_identifier_str oai:repositorio.unbosque.edu.co:20.500.12495/14348
network_acronym_str UNBOSQUE2
network_name_str Repositorio U. El Bosque
repository_id_str
dc.title.none.fl_str_mv Síntesis de un nuevo análogo inhibidor de farnesil pirofosfato sintasa para el tratamiento de la osteoporosis por medio de cribado virtual basado en ligando y estructura
dc.title.translated.none.fl_str_mv Synthesis of a novel farnesyl pyrophosphate synthase inhibitor analog for osteoporosis treatment by ligand- and structure-based virtual screening
title Síntesis de un nuevo análogo inhibidor de farnesil pirofosfato sintasa para el tratamiento de la osteoporosis por medio de cribado virtual basado en ligando y estructura
spellingShingle Síntesis de un nuevo análogo inhibidor de farnesil pirofosfato sintasa para el tratamiento de la osteoporosis por medio de cribado virtual basado en ligando y estructura
In silico
Bifosfonato
Alendronato de sodio
615.19
In silico
Bisphosphonate
Alendronate of sodium
title_short Síntesis de un nuevo análogo inhibidor de farnesil pirofosfato sintasa para el tratamiento de la osteoporosis por medio de cribado virtual basado en ligando y estructura
title_full Síntesis de un nuevo análogo inhibidor de farnesil pirofosfato sintasa para el tratamiento de la osteoporosis por medio de cribado virtual basado en ligando y estructura
title_fullStr Síntesis de un nuevo análogo inhibidor de farnesil pirofosfato sintasa para el tratamiento de la osteoporosis por medio de cribado virtual basado en ligando y estructura
title_full_unstemmed Síntesis de un nuevo análogo inhibidor de farnesil pirofosfato sintasa para el tratamiento de la osteoporosis por medio de cribado virtual basado en ligando y estructura
title_sort Síntesis de un nuevo análogo inhibidor de farnesil pirofosfato sintasa para el tratamiento de la osteoporosis por medio de cribado virtual basado en ligando y estructura
dc.creator.fl_str_mv Quiroga Sarmiento, Santiago
dc.contributor.advisor.none.fl_str_mv Guevara Pulido, James
dc.contributor.author.none.fl_str_mv Quiroga Sarmiento, Santiago
dc.subject.none.fl_str_mv In silico
Bifosfonato
Alendronato de sodio
topic In silico
Bifosfonato
Alendronato de sodio
615.19
In silico
Bisphosphonate
Alendronate of sodium
dc.subject.ddc.none.fl_str_mv 615.19
dc.subject.keywords.none.fl_str_mv In silico
Bisphosphonate
Alendronate of sodium
description La osteoporosis, una enfermedad de gran relevancia global, afecta a muchas personas y disminuye su calidad de vida. El tratamiento habitual incluye bifosfonatos, utilizados para reducir la regeneración ósea, pero su uso prolongado puede generar efectos adversos debido a la bioacumulación. Este estudio desarrolló un análogo del alendronato de sodio con sustituciones auxofóricas para mejorar la afinidad hacia el blanco terapéutico y reducir la toxicidad. Se encontró un modelo predictivo que superó la validación estadística y se sintetizó un análogo que mostró un IC50 de 273 nM y una energía de afinidad -6,504 kcal/mol demostrando una energía de afinidad, toxicidad, perfil de seguridad, %PPB y Caco-2 mejores que el alendronato de sodio.
publishDate 2025
dc.date.accessioned.none.fl_str_mv 2025-05-15T15:17:13Z
dc.date.available.none.fl_str_mv 2025-05-15T15:17:13Z
dc.date.issued.none.fl_str_mv 2025-04
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_7a1f
dc.type.local.none.fl_str_mv Tesis/Trabajo de grado - Monografía - Pregrado
dc.type.coar.none.fl_str_mv https://purl.org/coar/resource_type/c_7a1f
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/bachelorThesis
dc.type.coarversion.none.fl_str_mv https://purl.org/coar/version/c_ab4af688f83e57aa
format https://purl.org/coar/resource_type/c_7a1f
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12495/14348
dc.identifier.instname.spa.fl_str_mv Universidad El Bosque
dc.identifier.reponame.spa.fl_str_mv reponame:Repositorio Institucional Universidad El Bosque
dc.identifier.repourl.none.fl_str_mv repourl:https://repositorio.unbosque.edu.co
url https://hdl.handle.net/20.500.12495/14348
identifier_str_mv Universidad El Bosque
reponame:Repositorio Institucional Universidad El Bosque
repourl:https://repositorio.unbosque.edu.co
dc.language.iso.fl_str_mv spa
language spa
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2. C. D. la P. A Barrios, “Prevalencia de osteoporosis y osteopenia en pacientes laboralmente activos,” Scielo. Accessed: Jan. 20, 2025. [Online]. Available: https://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S2306-41022018000300131
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4. Martín, RM y PH Correa, Calidad ósea y terapia de la osteoporosis . Arq Bras Endocrinol Metabol, 2010. 54 (2): p. 186-99
5. Blair, HC, et al., Resorción ósea osteoclástica mediante una bomba de protones vacuolar polarizada . Science, 1989. 245 (4920): pág. 855-7
6. Raisz, LG, Patogenia de la osteoporosis: conceptos, conflictos y perspectivas . J Clin Invest, 2005. 115 (12): p. 3318-25
7. S. Maraka and K. A. Kennel, “Bisphosphonates for the prevention and treatment of osteoporosis,” BMJ: British Medical Journal, vol. 351, Sep. 2015, [Online]. Available: https://research.ebsco.com/linkprocessor/plink?id=2f09cd61-cd1b-33f4-8719-2c95648cede7
8. Blanco-González A, Cabezón A, Seco-González A, Conde-Torres D, Antelo-Riveiro P, Piñeiro Á, Garcia-Fandino R. The Role of AI in Drug Discovery: Challenges, Opportunities, and Strategies. Pharmaceuticals (Basel). 2023 Jun 18;16(6):891. doi: 10.3390/ph16060891. PMID: 37375838; PMCID: PMC10302890.
9. J. A. Gonzalez Amaya, D. Z. Cabrera, A. M. Matallana, K. G. Arevalo, and J. Guevara-Pulido, “In-silico design of new enalapril analogs (ACE inhibitors) using QSAR and molecular docking models,” Informatics in Medicine Unlocked, vol. 19, Jan. 2020, doi: 10.1016/j.imu.2020.100336.
10. Deissy N. Jaramillo, Diana Millán, James Guevara-Pulido, Design, synthesis and cytotoxic evaluation of a selective serotonin reuptake inhibitor (SSRI) by virtual screening, European Journal of Pharmaceutical Sciences, 10.1016/j.ejps.2023.106403, 183, (106403), (2023).
11. D. Zambrano, D. Millán, and J. Guevara-Pulido, “In silico design, synthesis and evaluation of a less toxic octinoxate alternative with suitable photoprotection properties,” European Journal of Pharmaceutical Sciences, vol. 180, Jan. 2023, doi: 10.1016/j.ejps.2022.106332.
12. D. N. Jaramillo, D. Millán, and J. Guevara-Pulido, “Design, synthesis and cytotoxic evaluation of a selective serotonin reuptake inhibitor (SSRI) by virtual screening,” European Journal of Pharmaceutical Sciences, vol. 183, Apr. 2023, doi: 10.1016/j.ejps.2023.106403.
13. M. Prieto, A. Niño, P. Acosta-Guzmán, and J. Guevara-Pulido, “Design and synthesis of a potential selective JAK-3 inhibitor for the treatment of rheumatoid arthritis using predictive QSAR models,” Informatics in Medicine Unlocked, vol. 45, Jan. 2024, doi: 10.1016/j.imu.2024.101464.
14. Rodriguez-Salazar, L., Guevara-Pulido, J., & Cifuentes, A. (2020). In Silico Design of a Peptide Receptor for Dopamine Recognition. Molecules, 25(23), 5509. https://doi.org/10.3390/molecules25235509
15. Fonseca-Benítez, V., Acosta-Guzmán, P., Sánchez, J. E., Alarcón, Z., Jiménez, R. A., & Guevara-Pulido, J. (2024). Design and Evaluation of NSAID Derivatives as AKR1C3 Inhibitors for Breast Cancer Treatment through Computer-Aided Drug Design and In Vitro Analysis. Molecules, 29(8), 1802. https://doi.org/10.3390/molecules29081802
16. S. Pirela-Ocando, A. Romero-Cabezas, and J. Guevara-Pulido, “Construction of a predictive model for the design of triptamin analogues with potential activity in Parkinson’s and Alzheimer’s diseases,” Informatics in Medicine Unlocked, vol. 43, Jan. 2023, doi: 10.1016/j.imu.2023.101413.
17. R. S. Luna, G. P. James, M. M. Esteban, and I. Francisco, “In-silico design of peptide receptor for carboxyhemoglobin recognition,” Informatics in Medicine Unlocked, vol. 14, pp. 1–5, Jan. 2019, doi: 10.1016/j.imu.2019.01.003.
18. M. Néstor, C. R. Tania, M. Ophir, and G. P. James, “A machine learning method for predicting the IC50 values of novel designed analogs of Non-Nucleoside Reverse-Transcriptase Inhibitors (NNRTIs) as potentially safer drugs,” Informatics in Medicine Unlocked, vol. 48, Jan. 2024, doi: 10.1016/j.imu.2024.101512.
19. J. A. González-Amaya, A. N. Niño-Colmenares, A. F. Cárdenas-Rodríguez, and J. Guevara-Pulido, “Artificial neural network-based QSAR model for predicting degradation techniques of pharmaceutical contaminants in water bodies with experimental verification,” Environ. Sci.: Water Res. Technol., vol. 10, no. 6, pp. 1492–1498, 2024, doi: 10.1039/D4EW00137K.
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37. “FICHA TÉCNICA-Alendronato de sodio-CIMA.” Accessed: Mar. 23, 2025. [Online]. Available: https://cima.aemps.es/cima/pdfs/ft/69193/FT_69193.pdf
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39. W. H. ;Newlander, K. A. ;Seefeld, M. A. ;Uzinskas, I. N. ;Dewolf, W. E. , Jr. ;Jakas, D. R. Miller, “Fab I Inhibitors,” 2004.
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spelling Guevara Pulido, JamesQuiroga Sarmiento, Santiago2025-05-15T15:17:13Z2025-05-15T15:17:13Z2025-04https://hdl.handle.net/20.500.12495/14348Universidad El Bosquereponame:Repositorio Institucional Universidad El Bosquerepourl:https://repositorio.unbosque.edu.coLa osteoporosis, una enfermedad de gran relevancia global, afecta a muchas personas y disminuye su calidad de vida. El tratamiento habitual incluye bifosfonatos, utilizados para reducir la regeneración ósea, pero su uso prolongado puede generar efectos adversos debido a la bioacumulación. Este estudio desarrolló un análogo del alendronato de sodio con sustituciones auxofóricas para mejorar la afinidad hacia el blanco terapéutico y reducir la toxicidad. Se encontró un modelo predictivo que superó la validación estadística y se sintetizó un análogo que mostró un IC50 de 273 nM y una energía de afinidad -6,504 kcal/mol demostrando una energía de afinidad, toxicidad, perfil de seguridad, %PPB y Caco-2 mejores que el alendronato de sodio.PregradoQuímico FarmacéuticoOsteoporosis, a disease of great global relevance, affects many people and diminishes their quality of life. The usual treatment includes bisphosphonates, used to reduce bone regeneration, but their prolonged use can generate adverse effects due to bioaccumulation. This study developed an alendronate sodium analog with auxophoric substitutions to improve affinity for the therapeutic target and reduce toxicity. A predictive model was found that passed statistical validation and an analog was synthesized that showed an IC50 of 273 nM and an affinity energy -6,504 kcal/mol demonstrating better affinity energy, toxicity, safety profile, %PPB and Caco-2 than alendronate sodium.application/pdfAttribution-NonCommercial-ShareAlike 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-sa/4.0/Acceso abiertohttps://purl.org/coar/access_right/c_abf2http://purl.org/coar/access_right/c_abf2In silicoBifosfonatoAlendronato de sodio615.19In silicoBisphosphonateAlendronate of sodiumSíntesis de un nuevo análogo inhibidor de farnesil pirofosfato sintasa para el tratamiento de la osteoporosis por medio de cribado virtual basado en ligando y estructuraSynthesis of a novel farnesyl pyrophosphate synthase inhibitor analog for osteoporosis treatment by ligand- and structure-based virtual screeningQuímica FarmacéuticaUniversidad El BosqueFacultad de CienciasTesis/Trabajo de grado - Monografía - Pregradohttps://purl.org/coar/resource_type/c_7a1fhttp://purl.org/coar/resource_type/c_7a1finfo:eu-repo/semantics/bachelorThesishttps://purl.org/coar/version/c_ab4af688f83e57aa1. National Institute of arthritis and musculoskeletal and skin diseases-NIH, “Causas y síntomas de la osteoporosis | NIAMS.” Accessed: Jan. 20, 2025. [Online]. Available: https://www.niams.nih.gov/health-topics/osteoporosis2. C. D. la P. A Barrios, “Prevalencia de osteoporosis y osteopenia en pacientes laboralmente activos,” Scielo. Accessed: Jan. 20, 2025. [Online]. Available: https://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S2306-410220180003001313. University of Rochester Medical Center, “Niveles bajos de estrógenos en la menopausia,” Health Encyclopedia. 2024. Accessed: Jan. 21, 2025. [Online]. Available: https://www.urmc.rochester.edu/encyclopedia/content?contenttypeid=85&contentid=p036524. Martín, RM y PH Correa, Calidad ósea y terapia de la osteoporosis . Arq Bras Endocrinol Metabol, 2010. 54 (2): p. 186-995. Blair, HC, et al., Resorción ósea osteoclástica mediante una bomba de protones vacuolar polarizada . Science, 1989. 245 (4920): pág. 855-76. Raisz, LG, Patogenia de la osteoporosis: conceptos, conflictos y perspectivas . J Clin Invest, 2005. 115 (12): p. 3318-257. S. Maraka and K. A. Kennel, “Bisphosphonates for the prevention and treatment of osteoporosis,” BMJ: British Medical Journal, vol. 351, Sep. 2015, [Online]. Available: https://research.ebsco.com/linkprocessor/plink?id=2f09cd61-cd1b-33f4-8719-2c95648cede78. Blanco-González A, Cabezón A, Seco-González A, Conde-Torres D, Antelo-Riveiro P, Piñeiro Á, Garcia-Fandino R. The Role of AI in Drug Discovery: Challenges, Opportunities, and Strategies. Pharmaceuticals (Basel). 2023 Jun 18;16(6):891. doi: 10.3390/ph16060891. PMID: 37375838; PMCID: PMC10302890.9. J. A. Gonzalez Amaya, D. Z. Cabrera, A. M. Matallana, K. G. Arevalo, and J. Guevara-Pulido, “In-silico design of new enalapril analogs (ACE inhibitors) using QSAR and molecular docking models,” Informatics in Medicine Unlocked, vol. 19, Jan. 2020, doi: 10.1016/j.imu.2020.100336.10. Deissy N. Jaramillo, Diana Millán, James Guevara-Pulido, Design, synthesis and cytotoxic evaluation of a selective serotonin reuptake inhibitor (SSRI) by virtual screening, European Journal of Pharmaceutical Sciences, 10.1016/j.ejps.2023.106403, 183, (106403), (2023).11. D. Zambrano, D. Millán, and J. Guevara-Pulido, “In silico design, synthesis and evaluation of a less toxic octinoxate alternative with suitable photoprotection properties,” European Journal of Pharmaceutical Sciences, vol. 180, Jan. 2023, doi: 10.1016/j.ejps.2022.106332.12. D. N. Jaramillo, D. Millán, and J. Guevara-Pulido, “Design, synthesis and cytotoxic evaluation of a selective serotonin reuptake inhibitor (SSRI) by virtual screening,” European Journal of Pharmaceutical Sciences, vol. 183, Apr. 2023, doi: 10.1016/j.ejps.2023.106403.13. M. Prieto, A. Niño, P. Acosta-Guzmán, and J. 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