Evaluación de la actividad tripanocida de elbasvir y glecaprevir y del efecto sobre la actividad de la enzima Cisteína sintasa de Trypanosoma cruzi in vitro

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dc.contributor.advisorTéllez Meneses, Jair Alexander
dc.contributor.advisorRomero Calderón, Ibeth Cristina
dc.contributor.authorChavarrio Cañas, Francy Milena
dc.contributor.researchgroupGrupo de enfermedades infecciosas - Pontificia Universidad Javerianaspa
dc.contributor.researchgroupGrupo Infecciones y Salud en el Trópico - Universidad Nacional de Colombia sede Bogotáspa
dc.contributor.researchgroupGrupo Zajuna Jwa Samu “Semilla del conocimiento” del Cesar - Universidad Nacional de Colombia sede la Pazspa
dc.date.accessioned2023-12-11T15:24:10Z
dc.date.available2023-12-11T15:24:10Z
dc.date.issued2023-12
dc.description.abstractLa enfermedad de Chagas (ECh), causada por el parasito protozoario Trypanosoma cruzi, es una enfermedad endémica y desatendida en las Américas. Debido a su compleja dinámica de transmisión, se ha convertido en un problema de salud pública en el mundo. Actualmente, se cuenta con dos medicamentos para su tratamiento, benznidazol (BNZ) y nifurtimox (NFX). Esos medicamentos distan de ser un tratamiento ideal debido a su baja eficacia durante la fase crónica, a los efectos secundarios severos que llevan a una alta tasa de abandono de la terapia, y la menor susceptibilidad que presentan algunas cepas del parásito a estos medicamentos. Esas dificultades en el tratamiento de la ECh, han llevado a la necesidad de buscar nuevas alternativas terapéuticas. En este sentido, la Cisteína sintasa de T. cruzi (TcCS) ha sido estudiada como potencial blanco terapéutico, sobre la cual, se han realizado análisis de biología computacional que han permitido la identificación de moléculas con una alta afinidad y estabilidad de unión al sitio activo de la TcCS, dentro de las cuales se encuentra el elbasvir (EBV) y el glecaprevir (GCV). La presente investigación tuvo como objetivo evaluar in vitro, la actividad tripanocida y el efecto inhibitorio de EBV y de GCV sobre la actividad de la enzima TcCS. El efecto tripanocida de los compuestos fue evaluado en los estadios tripomastigote y amastigote del parásito, la citotoxicidad en células Vero y el efecto sobre la actividad enzimática a partir de extractos de proteínas solubles del parásito. El compuesto EBV presentó actividad biológica contra T. cruzi con una CE50 de 24.22 μM sobre el estadio tripomastigotes y una CI50 de 7.59 μM sobre el amastigote; con un índice de selectividad (IS) estimado de al menos 2.06 en el estadio infectivo y de al menos 6.58 sobre el estadio intracelular. Por su parte, GCV no mostró actividad biológica contra T. cruzi, y su citotoxicidad fue intermedia (CC50: 134.4 μM). Los compuestos evaluados no presentaron una inhibición selectiva de la actividad enzimática de TcCS. En conclusión, EBV presenta una actividad biológica principalmente contra el estadio amastigote de T. cruzi, lo cual hace de éste un posible compuesto líder para el desarrollo de nuevos tratamientos contra la ECh. (Texto tomado de la fuente)spa
dc.description.abstractChagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, is an endemic and neglected disease in the Americas. Due to its complex transmission dynamics, it has become a public health problem in the world. Currently, there are two medications for its treatment, benznidazole (BNZ) and nifurtimox (NFX). These medications are far from being an ideal treatment due to their low effectiveness during the chronic phase, severe side effects that lead to a high rate of abandonment of therapy, and the lower susceptibility of some strains of the parasite to these medications. These difficulties in the treatment of CD have led to the need to search for new therapeutic alternatives. In this sense, T. cruzi Cysteine synthase (TcCS) has been studied as a potential therapeutic target, on which computational biology analyzes have been conducted that have allowed the identification of molecules with high affinity and stability of binding to the TcCS active site, among which are elbasvir (EBV) and glecaprevir (GCV). The aim of this research was to evaluate in vitro, trypanocidal activity and inhibitory effect of EBV and GCV on the activity of the TcCS enzyme. The trypanocidal effect of the compounds was evaluated in trypomastigote and amastigote stages of the parasite, cytotoxicity in Vero cells and effect on the enzymatic activity from soluble protein extracts of the parasite. The EBV compound presented biological activity against T. cruzi with an EC50 of 24.22 μM on trypomastigote stage and an IC50 of 7.59 μM on amastigote; with an estimated selectivity index (SI) of at least 2.06 in the infective stage and at least 6.58 in the intracellular stage. For its part, GCV did not show biological activity against T. cruzi, and its cytotoxicity was intermediate (CC50: 134.4 μM). The compounds evaluated did not present a selective inhibition of the enzymatic activity of TcCS. In conclusion, EBV presents biological activity mainly against amastigote stage of T. cruzi, which makes it a possible lead compound for the development of new treatments against CD.eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Ciencias - Microbiologíaspa
dc.description.researchareaBiotecnología en saludspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/85063
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Ciencias - Maestría en Ciencias - Microbiologíaspa
dc.relation.referencesAguilera, E., Varela, J., Serna, E., Torres, S., Yaluff, G., De Bilbao, N. V., Cerecetto, H., Alvarez, G., & González, M. (2018). Looking for combination of benznidazole and trypanosoma cruzitriosephosphate isomerase inhibitors for chagas disease treatment. Memorias Do Instituto Oswaldo Cruz, 113(3), 153–160. https://doi.org/10.1590/0074-02760170267spa
dc.relation.referencesAsselah, T., Pol, S., Hezode, C., Loustaud-Ratti, V., Leroy, V., Ahmed, S. N. S., Ozenne, V., Bronowicki, J. P., Larrey, D., Tran, A., Alric, L., Nguyen-Khac, E., Robertson, M. N., Hanna, G. J., Brown, D., Asante-Appiah, E., Su, F. H., Hwang, P., Hall, J. D., … Serfaty, L. (2020). Efficacy and safety of elbasvir/grazoprevir for 8 or 12 weeks for hepatitis C virus genotype 4 infection: A randomized study. Liver International, 40(5), 1042–1051. https://doi.org/10.1111/liv.14313spa
dc.relation.referencesAtwood, J. A., Weatherly, D. B., Minning, T. A., Bundy, B., Cavola, C., Opperdoes, F. R., Orlando, R., & Tarleton, R. L. (2005). Microbiology: The Trypanosoma cruzi proteome. Science, 309(5733), 473–476. https://doi.org/10.1126/science.1110289spa
dc.relation.referencesBahia, M. T., De Figueiredo Diniz, L. D. F., & Mosqueira, V. C. F. (2014). Therapeutical approaches under investigation for treatment of Chagas disease. Expert Opinion on Investigational Drugs, 23(9), 1225–1237. https://doi.org/10.1517/13543784.2014.922952spa
dc.relation.referencesBalasubramaniam, M., & Reis, R. J. S. (2020). Computational target-based drug repurposing of elbasvir, an antiviral drug predicted to bind multiple SARS-CoV-2 proteins. ChemRxiv : The Preprint Server for Chemistry. https://doi.org/10.26434/chemrxiv.12084822spa
dc.relation.referencesBeaumier, C. M., Gillespie, P. M., Strych, U., Hayward, T., Hotez, P. J., & Bottazzi, M. E. (2016). Status of vaccine research and development of vaccines for Chagas disease. Vaccine, 34(26), 2996–3000. https://doi.org/10.1016/j.vaccine.2016.03.074spa
dc.relation.referencesBeer, M. F., Frank, F. M., Germán Elso, O., Ernesto Bivona, A., Cerny, N., Giberti, G., Luis Malchiodi, E., Susana Martino, V., Alonso, M. R., Patricia Sülsen, V., & Cazorla, S. I. (2016). Trypanocidal and leishmanicidal activities of flavonoids isolated from Stevia satureiifolia var. satureiifolia. Pharmaceutical Biology, 54(10), 2188–2195. https://doi.org/10.3109/13880209.2016.1150304spa
dc.relation.referencesBeltran-Hortelano, I., Alcolea, V., Font, M., & Pérez-Silanes, S. (2022). Examination of multiple Trypanosoma cruzi targets in a new drug discovery approach for Chagas disease. Bioorganic & Medicinal Chemistry, 58, 116577. https://doi.org/10.1016/j.bmc.2021.116577spa
dc.relation.referencesBern, C. (2011). Antitrypanosomal Therapy for Chronic Chagas’ Disease. New England Journal of Medicine, 365(13), 1258–1259. https://doi.org/10.1056/nejmc1108653spa
dc.relation.referencesBern, C., Messenger, L. A., Whitman, J. D., & Maguire, J. H. (2019). Chagas disease in the united states: A public health approach. Clinical Microbiology Reviews, 33(1), 1–42. https://doi.org/10.1128/CMR.00023-19spa
dc.relation.referencesBerná, L., Chiribao, M. L., Greif, G., Rodriguez, M., Alvarez-Valin, F., & Robello, C. (2017). Transcriptomic analysis reveals metabolic switches and surface remodeling as key processes for stage transition in trypanosoma cruzi. PeerJ, 2017(3), 1–32. https://doi.org/10.7717/peerj.3017spa
dc.relation.referencesBero, J., Ganfon, H., Jonville, M. C., Frédérich, M., Gbaguidi, F., DeMol, P., Moudachirou, M., & Quetin-Leclercq, J. (2009). In vitro antiplasmodial activity of plants used in Benin in traditional medicine to treat malaria. Journal of Ethnopharmacology, 122(3), 439–444. https://doi.org/10.1016/j.jep.2009.02.004spa
dc.relation.referencesBero, J., Hannaert, V., Chataigné, G., Hérent, M. F., & Quetin-Leclercq, J. (2011). In vitro antitrypanosomal and antileishmanial activity of plants used in Benin in traditional medicine and bio-guided fractionation of the most active extract. Journal of Ethnopharmacology, 137(2), 998–1002. https://doi.org/10.1016/j.jep.2011.07.022spa
dc.relation.referencesBreckenridge, A., & Jacob, R. (2019). Overcoming the legal and regulatory barriers to drug repurposing. Nature Reviews. Drug Discovery, 18(1), 1–2. https://doi.org/10.1038/nrd.2018.92spa
dc.relation.referencesCada, D. J., Editor, F., & Kim, A. P. (2016). Elbasvir / Grazoprevir. 51(8), 665–686. https://doi.org/10.1310/hpj5108spa
dc.relation.referencesCampos, M. C. O., Castro-Pinto, D. B., Ribeiro, G. A., Berredo-Pinho, M. M., Gomes, L. H. F., Da Silva Bellieny, M. S., Goulart, C. M., Echevarria, Á., & Leon, L. L. (2013). P-glycoprotein efflux pump plays an important role in Trypanosoma cruzi drug resistance. Parasitology Research, 112(6), 2341–2351. https://doi.org/10.1007/s00436-013-3398-zspa
dc.relation.referencesCanepa, G. E., Bouvier, L. A., Miranda, M. R., Uttaro, A. D., & Pereira, C. A. (2009). Characterization of Trypanosoma cruzi L-cysteine transport mechanisms and their adaptive regulation. FEMS Microbiology Letters, 292(1), 27–32. https://doi.org/10.1111/j.1574-6968.2008.01467.xspa
dc.relation.referencesCDC, C. of D. C. and P. (2019). Parasites - American Trypanosomiasis (also known as Chagas Disease). https://www.cdc.gov/parasites/chagas/spa
dc.relation.referencesChatelain, E. (2015). Chagas disease drug discovery: Toward a new era. Journal of Biomolecular Screening, 20(1), 22–35. https://doi.org/10.1177/1087057114550585spa
dc.relation.referencesChtita, S., Belhassan, A., Aouidate, A., Belaidi, S., Bouachrine, M., & Lakhlifi, T. (2021). Discovery of Potent SARS-CoV-2 Inhibitors from Approved Antiviral Drugs via Docking and Virtual Screening. Combinatorial Chemistry & High Throughput Screening, 24(3), 441–454. https://doi.org/10.2174/1386207323999200730205447spa
dc.relation.referencesCook, S. E., Vogel, H., Castillo, D., Olsen, M., Pedersen, N., & Murphy, B. G. (2021). Investigation of monotherapy and combined anticoronaviral therapies against feline coronavirus serotype II in vitro. Journal of Feline Medicine and Surgery, 24(10), 943–953. https://doi.org/10.1177/1098612X211048647spa
dc.relation.referencesCrespillo-Andújar, C., Chamorro-Tojeiro, S., Norman, F., Monge-Maillo, B., López-Vélez, R., & Pérez-Molina, J. A. (2018). Toxicity of nifurtimox as second-line treatment after benznidazole intolerance in patients with chronic Chagas disease: when available options fail. Clinical Microbiology and Infection, 24(12), 1344.e1-1344.e4. https://doi.org/10.1016/j.cmi.2018.06.006spa
dc.relation.referencesDe Andrade, P., Galo, O. A., Carvalho, M. R., Lopes, C. D., Carneiro, Z. A., Sesti-Costa, R., De Melo, E. B., Silva, J. S., & Carvalho, I. (2015). 1,2,3-Triazole-based analogue of benznidazole displays remarkable activity against Trypanosoma cruzi. Bioorganic and Medicinal Chemistry, 23(21), 6815–6826. https://doi.org/10.1016/j.bmc.2015.10.008spa
dc.relation.referencesde Oliveira, R. G., Cruz, L. R., Mollo, M. C., Dias, L. C., & Kratz, J. M. (2021). Chagas Disease Drug Discovery in Latin America—A Mini Review of Antiparasitic Agents Explored Between 2010 and 2021. Frontiers in Chemistry, 9(October), 1–7. https://doi.org/10.3389/fchem.2021.771143spa
dc.relation.referencesde Souza, W. (2009). Structural organization of Trypanosoma cruzi. Memorias Do Instituto Oswaldo Cruz, 104(SUPPL. 1), 89–100. https://doi.org/10.1590/s0074-02762009000900014spa
dc.relation.referencesDecuypere, S., Vanaerschot, M., Brunker, K., Imamura, H., Müller, S., Khanal, B., Rijal, S., Dujardin, J. C., & Coombs, G. H. (2012). Molecular mechanisms of drug resistance in natural leishmania populations vary with genetic background. PLoS Neglected Tropical Diseases, 6(2). https://doi.org/10.1371/journal.pntd.0001514spa
dc.relation.referencesDharavath, S., Vijayan, R., Kumari, K., Tomar, P., & Gourinath, S. (2020). Crystal structure of O-Acetylserine sulfhydralase (OASS) isoform 3 from Entamoeba histolytica: Pharmacophore-based virtual screening and validation of novel inhibitors. European Journal of Medicinal Chemistry, 192, 112157. https://doi.org/10.1016/j.ejmech.2020.112157spa
dc.relation.referencesEkins, S., Williams, A. J., Krasowski, M. D., & Freundlich, J. S. (2011). In silico repositioning of approved drugs for rare and neglected diseases. Drug Discovery Today, 16(7–8), 298–310. https://doi.org/10.1016/j.drudis.2011.02.016spa
dc.relation.referencesEl-Sayed, N. M., Myler, P. J., Bartholomeu, D. C., Nilsson, D., Aggarwal, G., Tran, A. N., Ghedin, E., Worthey, E. A., Delcher, A. L., Blandin, G., Westenberger, S. J., Caler, E., Cerqueira, G. C., Branche, C., Haas, B., Anupama, A., Arner, E., Åslund, L., Attipoe, P., … Andersson, B. (2005). The genome sequence of Trypanosoma cruzi, etiologic agent of chagas disease. Science, 309(5733). https://doi.org/10.1126/science.1112631spa
dc.relation.referencesEuropean Medicines Agency. (2016). Zepatier: Assessment Report (Vol. 44, Issue May). https://www.ema.europa.eu/en/documents/assessment-report/zepatier-epar-public-assessment-report_en.pdfspa
dc.relation.referencesFyfe, P. K., Westrop, G. D., Ramos, T., Müller, S., Coombs, G. H., & Hunter, W. N. (2012). Structure of Leishmania major cysteine synthase. Acta Crystallographica Section F: Structural Biology and Crystallization Communications, 68(7), 738–743. https://doi.org/10.1107/S1744309112019124spa
dc.relation.referencesGammeltoft, K. A., Zhou, Y., Hernandez, C. R. D., Galli, A., Offersgaard, A., Costa, R., Pham, L. V., Fahnøe, U., Feng, S., Scheel, T. K. H., Ramirez, S., Bukh, J., & Gottwein, J. M. (2021). Hepatitis c virus protease inhibitors show differential efficacy and interactions with Remdesivir for treatment of SARS-CoV-2 in Vitro. Antimicrobial Agents and Chemotherapy, 65(9), 1–24. https://doi.org/10.1128/AAC.02680-20spa
dc.relation.referencesGarcía-Huertas, P., Mejía-Jaramillo, A. M., González, L., & Triana-Chávez, O. (2017). Transcriptome and Functional Genomics Reveal the Participation of Adenine Phosphoribosyltransferase in Trypanosoma cruzi Resistance to Benznidazole. Journal of Cellular Biochemistry, 118(7), 1936–1945. https://doi.org/10.1002/jcb.25978spa
dc.relation.referencesGarcía-Huertas, P., Mejía-Jaramillo, A. M., Machado, C. R., Guimarães, A. C., & Triana-Chávez, O. (2017). Prostaglandin F2α synthase in trypanosoma cruzi plays critical roles in oxidative stress and susceptibility to benznidazole. Royal Society Open Science, 4(9). https://doi.org/10.1098/rsos.170773spa
dc.relation.referencesGhosh, A. K., Samanta, I., Mondal, A., & Liu, W. R. (2019). Covalent Inhibition in Drug Discovery. ChemMedChem, 14(9), 889–906. https://doi.org/10.1002/cmdc.201900107spa
dc.relation.referencesGonzález, L., García-Huertas, P., Triana-Chávez, O., García, G. A., Murta, S. M. F., & Mejía-Jaramillo, A. M. (2017). Aldo-keto reductase and alcohol dehydrogenase contribute to benznidazole natural resistance in Trypanosoma cruzi. Molecular Microbiology, 106(5), 704–718. https://doi.org/10.1111/mmi.13830spa
dc.relation.referencesGopal, G. J., & Kumar, A. (2013). Strategies for the production of recombinant protein in escherichia coli. Protein Journal, 32(6), 419–425. https://doi.org/10.1007/s10930-013-9502-5spa
dc.relation.referencesGuarner, J. (2019). Chagas disease as example of a reemerging parasite. Seminars in Diagnostic Pathology, 36(3), 164–169. https://doi.org/10.1053/j.semdp.2019.04.008spa
dc.relation.referencesHall, B. S., & Wilkinson, S. R. (2012). Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation. Antimicrobial Agents and Chemotherapy, 56(1), 115–123. https://doi.org/10.1128/AAC.05135-11spa
dc.relation.referencesHorner, S. M., & Gale, M. (2013). Regulation of hepatic innate immunity by hepatitis C virus. Nature Medicine, 19(7), 879–888. https://doi.org/10.1038/nm.3253spa
dc.relation.referencesHuličiak, M., Vokřál, I., Holas, O., Martinec, O., Štaud, F., & Červený, L. (2022). Evaluation of the Potency of Anti-HIV and Anti-HCV Drugs to Inhibit P-Glycoprotein Mediated Efflux of Digoxin in Caco-2 Cell Line and Human Precision-Cut Intestinal Slices. Pharmaceuticals, 15(2). https://doi.org/10.3390/ph15020242spa
dc.relation.referencesIbrahim, M. A. A., Abdeljawaad, K. A. A., Jaragh-Alhadad, L. A., Oraby, H. F., Atia, M. A. M., Alzahrani, O. R., Mekhemer, G. A. H., Moustafa, M. F., Shawky, A. M., Sidhom, P. A., & Abdelrahman, A. H. M. (2023). Potential drug candidates as P-glycoprotein inhibitors to reverse multidrug resistance in cancer: an in silico drug discovery study. Journal of Biomolecular Structure & Dynamics, 1–16. https://doi.org/10.1080/07391102.2023.2176360spa
dc.relation.referencesINS, I. N. de S. (2023). Informe de evento: CHAGAS. https://www.ins.gov.co/buscador-eventos/Paginas/Info-Evento.aspxspa
dc.relation.referencesIsah, M. B., Ibrahim, M. A., Mohammed, A., Aliyu, A. B., Masola, B., & Coetzer, T. H. T. (2016). A systematic review of pentacyclic triterpenes and their derivatives as chemotherapeutic agents against tropical parasitic diseases. Parasitology, 143(10), 1219–1231. https://doi.org/10.1017/S0031182016000718spa
dc.relation.referencesJackson, Y., Wyssa, B., & Chappuis, F. (2020). Tolerance to nifurtimox and benznidazole in adult patients with chronic Chagas’ disease. Journal of Antimicrobial Chemotherapy, 75(3), 690–696. https://doi.org/10.1093/jac/dkz473spa
dc.relation.referencesJean, V., Poyraz, Ö., Saxena, S., Schnell, R., Yogeeswari, P., Schneider, G., & Sriram, D. (2013). Discovery of novel inhibitors targeting the Mycobacterium tuberculosis O-acetylserine sulfhydrylase (CysK1) using virtual high-throughput screening. Bioorganic and Medicinal Chemistry Letters, 23(5), 1182–1186. https://doi.org/10.1016/j.bmcl.2013.01.031spa
dc.relation.referencesJubair, N., Rajagopal, M., Chinnappan, S., Abdullah, N. B., & Fatima, A. (2021). Review on the Antibacterial Mechanism of Plant-Derived Compounds against Multidrug-Resistant Bacteria (MDR). Evidence-Based Complementary and Alternative Medicine, 2021. https://doi.org/10.1155/2021/3663315spa
dc.relation.referencesKosloski, M. P., Bow, D. A. J., Kikuchi, R., Wang, H., Kim, E. J., Marsh, K., Mensa, F., Kort, J., & Liu, W. (2019). Translation of in vitro transport inhibition studies to clinical drug-drug interactions for glecaprevir and pibrentasvirs. Journal of Pharmacology and Experimental Therapeutics, 370(2), 278–287. https://doi.org/10.1124/jpet.119.256966spa
dc.relation.referencesKratz, J. M. (2019). Drug discovery for chagas disease: A viewpoint. Acta Tropica, 198(July). https://doi.org/10.1016/j.actatropica.2019.105107spa
dc.relation.referencesLamb, Y. N. (2017). Glecaprevir/Pibrentasvir: First Global Approval. Drugs, 77(16), 1797–1804. https://doi.org/10.1007/s40265-017-0817-yspa
dc.relation.referencesLee, B. Y., Bacon, K. M., Bottazzi, M. E., & Hotez, P. J. (2013). Global economic burden of Chagas disease: a computational simulation model. The Lancet. Infectious Diseases, 13(4), 342–348. https://doi.org/10.1016/S1473-3099(13)70002-1spa
dc.relation.referencesLeite, D. I., Fontes, F. de V., Bastos, M. M., Hoelz, L. V. B., Bianco, M. da C. A. D., de Oliveira, A. P., da Silva, P. B., da Silva, C. F., Batista, D. da G. J., da Gama, A. N. S., Peres, R. B., Villar, J. D. F., Soeiro, M. de N. C., & Boechat, N. (2018). New 1,2,3-triazole-based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations. Chemical Biology and Drug Design, 92(3), 1670–1682. https://doi.org/10.1111/cbdd.13333spa
dc.relation.referencesLi, Y., Shah-Simpson, S., Okrah, K., Belew, A. T., Choi, J., Caradonna, K. L., Padmanabhan, P., Ndegwa, D. M., Temanni, M. R., Corrada Bravo, H., El-Sayed, N. M., & Burleigh, B. A. (2016). Transcriptome Remodeling in Trypanosoma cruzi and Human Cells during Intracellular Infection. PLoS Pathogens, 12(4), 1–30. https://doi.org/10.1371/journal.ppat.1005511spa
dc.relation.referencesLidani, K. C. F., Andrade, F. A., Bavia, L., Damasceno, F. S., Beltrame, M. H., Messias-Reason, I. J., & Sandri, T. L. (2019). Chagas disease: From discovery to a worldwide health problem. Journal of Physical Oceanography, 49(6), 1–13. https://doi.org/10.3389/fpubh.2019.00166spa
dc.relation.referencesLima, C. R., Carels, N., Guimaraes, A. C. R., Tufféry, P., & Derreumaux, P. (2016). In silico structural characterization of protein targets for drug development against Trypanosoma cruzi. Journal of Molecular Modeling, 22(10). https://doi.org/10.1007/s00894-016-3115-9spa
dc.relation.referencesLiu, R., Curry, S., McMonagle, P., Yeh, W. W., Ludmerer, S. W., Jumes, P. A., Marshall, W. L., Kong, S., Ingravallo, P., Black, S., Pak, I., DiNubile, M. J., & Howe, A. Y. M. (2015). Susceptibilities of genotype 1a, 1b, and 3 hepatitis C virus variants to the NS5A inhibitor elbasvir. Antimicrobial Agents and Chemotherapy, 59(11), 6922–6929. https://doi.org/10.1128/AAC.01390-15spa
dc.relation.referencesMady, C., Ianni, B. M., & de Souza, J. L. (2008). Benznidazole and Chagas disease: Can an old drug be the answer to an old problem? Expert Opinion on Investigational Drugs, 17(10), 1427–1433. https://doi.org/10.1517/13543784.17.10.1427spa
dc.relation.referencesMagalhães, J., Franko, N., Annunziato, G., Welch, M., Dolan, S. K., Bruno, A., Mozzarelli, A., Armao, S., Jirgensons, A., Pieroni, M., Costantino, G., & Campanini, B. (2018). Discovery of novel fragments inhibiting O-acetylserine sulphhydrylase by combining scaffold hopping and ligand–based drug design. Journal of Enzyme Inhibition and Medicinal Chemistry, 33(1), 1444–1452. https://doi.org/10.1080/14756366.2018.1512596spa
dc.relation.referencesMalone, C. J., Nevis, I., Fernández, E., & Sanchez, A. (2021). A rapid review on the efficacy and safety of pharmacological treatments for chagas disease. Tropical Medicine and Infectious Disease, 6(3). https://doi.org/10.3390/tropicalmed6030128spa
dc.relation.referencesMarciano, D., Santana, M., & Nowicki, C. (2012). Functional characterization of enzymes involved in cysteine biosynthesis and H2S production in Trypanosoma cruzi. Molecular and Biochemical Parasitology, 185(2), 114–120. https://doi.org/10.1016/j.molbiopara.2012.07.009spa
dc.relation.referencesMartín-Escolano, J., Medina-Carmona, E., & Martín-Escolano, R. (2020). Chagas Disease: Current View of an Ancient and Global Chemotherapy Challenge. ACS Infectious Diseases, 6(11), 2830–2843. https://doi.org/10.1021/acsinfecdis.0c00353spa
dc.relation.referencesMatsuo, A. L., Silva, L. S., Torrecilhas, A. C., Pascoalino, B. S., Ramos, T. C., Rodrigues, E. G., Schenkman, S., Caires, A. C. F., & Travassos, L. R. (2010). In vitro and in vivo trypanocidal effects of the cyclopalladated compound 7a, a drug candidate for treatment of Chagas’ disease. Antimicrobial Agents and Chemotherapy, 54(8), 3318–3325. https://doi.org/10.1128/AAC.00323-10spa
dc.relation.referencesMaya, J. D., Cassels, B. K., Iturriaga-Vásquez, P., Ferreira, J., Faúndez, M., Galanti, N., Ferreira, A., & Morello, A. (2007). Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host. Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology, 146(4), 601–620. https://doi.org/10.1016/j.cbpa.2006.03.004spa
dc.relation.referencesMedChemExpress. (2023). Master of Bioactive Molecules. https://www.medchemexpress.com/spa
dc.relation.referencesMeira, C. S., Barbosa-Filho, J. M., Lanfredi-Rangel, A., Guimarães, E. T., Moreira, D. R. M., & Soares, M. B. P. (2016). Antiparasitic evaluation of betulinic acid derivatives reveals effective and selective anti-Trypanosoma cruzi inhibitors. Experimental Parasitology, 166, 108–115. https://doi.org/10.1016/j.exppara.2016.04.007spa
dc.relation.referencesMejía-Jaramillo, A. M., Fernández, G. J., Palacio, L., & Triana-Chávez, O. (2011). Gene expression study using real-time PCR identifies an NTR gene as a major marker of resistance to benznidazole in Trypanosoma cruzi. Parasites and Vectors, 4(1), 1–12. https://doi.org/10.1186/1756-3305-4-169spa
dc.relation.referencesMejia, A. M., Hall, B. S., Taylor, M. C., Gómez-Palacio, A., Wilkinson, S. R., Triana-Chávez, O., & Kelly, J. M. (2012). Benznidazole-resistance in trypanosoma cruzi is a readily acquired trait that can arise independently in a single population. Journal of Infectious Diseases, 206(2), 220–228. https://doi.org/10.1093/infdis/jis331spa
dc.relation.referencesMerck Sharp & Dohme Corp. (2016). ZEPATIER- elbasvir and grazoprevir tablet, film coated. https://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_pi.pdfspa
dc.relation.referencesMilani, M., Donalisio, M., Bonotto, R. M., Schneider, E., Arduino, I., Boni, F., Lembo, D., Marcello, A., & Mastrangelo, E. (2021). Combined in silico and in vitro approaches identified the antipsychotic drug lurasidone and the antiviral drug elbasvir as SARS-CoV2 and HCoV-OC43 inhibitors. Antiviral Research, 189, 105055. https://doi.org/10.1016/j.antiviral.2021.105055spa
dc.relation.referencesMinning, T. A., Weatherly, D. B., Atwood, J., Orlando, R., & Tarleton, R. L. (2009). The steady-state transcriptome of the four major life-cycle stages of Trypanosoma cruzi. BMC Genomics, 10. https://doi.org/10.1186/1471-2164-10-370spa
dc.relation.referencesMoreno, É. M., Leal, S. M., Stashenko, E. E., & García, L. T. (2018). Induction of programmed cell death in Trypanosoma cruzi by Lippia alba essential oils and their major and synergistic terpenes (citral, limonene and caryophyllene oxide). BMC Complementary and Alternative Medicine, 18(1), 1–16. https://doi.org/10.1186/s12906-018-2293-7spa
dc.relation.referencesMüller Kratz, J., Garcia Bournissen, F., Forsyth, C. J., & Sosa-Estani, S. (2018). Clinical and pharmacological profile of benznidazole for treatment of Chagas disease. In Expert Review of Clinical Pharmacology (Vol. 11, Issue 10). Taylor & Francis. https://doi.org/10.1080/17512433.2018.1509704spa
dc.relation.referencesNg, T., Tripathi, R., Dekhtyar, T., Krishnan, P., Schnell, G., Beyer, J., Mcdaniel, K. F., & Ma, J. (2018). In Vitro Antiviral Activity and Resistance Profile of the Next-Generation HCV NS3-4A Protease Inhibitor Glecaprevir. Antimicrobial Agents and Chemotherapy, 62(1), 1–16.spa
dc.relation.referencesNozaki, T., Ali, V., & Tokoro, M. (2005). Sulfur-containing amino acid metabolism in parasitic protozoa. In Advances in Parasitology (Vol. 60, Issue 05). Elsevier Masson SAS. https://doi.org/10.1016/S0065-308X(05)60001-2spa
dc.relation.referencesNozaki, T., Shigeta, Y., Saito-Nakano, Y., Imada, M., & Kruger, W. D. (2001). Characterization of transsulfuration and cysteine biosynthetic pathways in the protozoan hemoflagellate, Trypanosoma cruzi: Isolation and molecular characterization of cystathionine β-synthase and serine acetyltransferase from trypanosoma. Journal of Biological Chemistry, 276(9), 6516–6523. https://doi.org/10.1074/jbc.M009774200spa
dc.relation.referencesNunes, M. C. P., Dones, W., Morillo, C. A., Encina, J. J., & Ribeiro, A. L. (2013). Chagas disease: An overview of clinical and epidemiological aspects. Journal of the American College of Cardiology, 62(9), 767–776. https://doi.org/10.1016/j.jacc.2013.05.046spa
dc.relation.referencesNúñez-Vergara, L. J., Squella, J. A., Aldunate, J., Letelier, M. E., Bollo, S., Repetto, Y., Morello, A., & Spencer, P. L. (1997). Nitro radical anion formation from nifurtimox. Part 1: Biological evidences in Trypanosoma cruzi. Bioelectrochemistry and Bioenergetics, 43(1), 151–155. https://doi.org/10.1016/S0302-4598(96)05188-4spa
dc.relation.referencesNwaka, S., & Hudson, A. (2006). Innovative lead discovery strategies for tropical diseases. Nature Reviews Drug Discovery, 5(11), 941–955. https://doi.org/10.1038/nrd2144spa
dc.relation.referencesOlivera, M. J., & Buitrago, G. (2020). Economic costs of Chagas disease in Colombia in 2017: A social perspective. International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases, 91, 196–201. https://doi.org/10.1016/j.ijid.2019.11.022spa
dc.relation.referencesOlivera, M. J., Cucunubá, Z. M., Valencia-Hernández, C. A., Herazo, R., Agreda-Rudenko, D., Flórez, C., Duque, S., & Nicholls, R. S. (2017). Risk factors for treatment interruption and severe adverse effects to benznidazole in adult patients with Chagas disease. PLoS ONE, 12(9), 1–13. https://doi.org/10.1371/journal.pone.0185033spa
dc.relation.referencesOPS, O. P. de la S. (2022). Chagas disease. https://www.paho.org/en/documents/factsheet-chagas-disease-americas-public-health-workersspa
dc.relation.referencesPardo-rodriguez, D., Cifuentes-l, A., Bravo-espejo, J., Romero, I., Robles, J., Cuervo, C., Mej, S. M., & Tellez, J. (2023). Lupeol Acetate and α -Amyrin Terpenes Activity against Trypanosoma cruzi : Insights into Toxicity and Potential Mechanisms of Action.spa
dc.relation.referencesPardo-Rodriguez, D., Lasso, P., Mateus, J., Mendez, J., Puerta, C. J., Cuéllar, A., Robles, J., & Cuervo, C. (2022). A terpenoid-rich extract from Clethra fimbriata exhibits anti-Trypanosoma cruzi activity and induces T cell cytokine production. Heliyon, 8(3). https://doi.org/10.1016/j.heliyon.2022.e09182spa
dc.relation.referencesPavia, P. X., Thomas, M. C., López, M. C., & Puerta, C. J. (2012). Molecular characterization of the short interspersed repetitive element SIRE in the six discrete typing units (DTUs) of Trypanosoma cruzi. Experimental Parasitology, 132(2), 144–150. https://doi.org/10.1016/j.exppara.2012.06.007spa
dc.relation.referencesPech-Canul, Á. D. L. C., Monteón, V., & Solís-Oviedo, R. L. (2017). A Brief View of the Surface Membrane Proteins from Trypanosoma cruzi. Journal of Parasitology Research, 2017. https://doi.org/10.1155/2017/3751403spa
dc.relation.referencesPérez-Molina, J. A., Crespillo-Andújar, C., Bosch-Nicolau, P., & Molina, I. (2021). Trypanocidal treatment of Chagas disease. Enfermedades Infecciosas y Microbiologia Clinica (English Ed.), 39(9), 458–470. https://doi.org/10.1016/j.eimce.2020.04.012spa
dc.relation.referencesPijnenburg, D. W. M., van Seyen, M., Abbink, E. J., Colbers, A., Drenth, J. P. H., & Burger, D. M. (2020). Pharmacokinetic similarity demonstrated after crushing of the elbasvir/grazoprevir fixed-dose combination tablet for HCV infection. Journal of Antimicrobial Chemotherapy, 75(9), 2661–2665. https://doi.org/10.1093/jac/dkaa230spa
dc.relation.referencesPink, R., Hudson, A., Mouriès, M. A., & Bendig, M. (2005). Opportunities and challenges in antiparasitic drug discovery. Nature Reviews Drug Discovery, 4(9), 727–740. https://doi.org/10.1038/nrd1824spa
dc.relation.referencesPortillo, S., Zepeda, B. G., Iniguez, E., Olivas, J. J., Karimi, N. H., Moreira, O. C., Marques, A. F., Michael, K., Maldonado, R. A., & Almeida, I. C. (2019). A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease. Npj Vaccines, 4(1). https://doi.org/10.1038/s41541-019-0107-7spa
dc.relation.referencesPrata, A. (2001). Clinical and epidemiological aspects of Chagas disease. Lancet Infectious Diseases, 1(2), 92–100. https://doi.org/10.1016/S1473-3099(01)00065-2spa
dc.relation.referencesQiagen. (2011). QIA express ® Ni-NTA Fast Start Handbook For purification and detection of recombinant Sample & Assay Technologies QIAGEN Sample and Assay Technologies (Issue July). file:///C:/Users/fmile/Downloads/EN-QIAexpress-Ni-NTA-Fast-Start-Handbook (2).pdfspa
dc.relation.referencesRamírez, J. D., & Hernández, C. (2018). Trypanosoma cruzi I: Towards the need of genetic subdivision?, Part II. Acta Tropica, 184, 53–58. https://doi.org/10.1016/j.actatropica.2017.05.005spa
dc.relation.referencesRassi, A., Rassi, A., & Marin-Neto, J. A. (2010). Chagas disease. The Lancet, 375(9723), 1388–1402. https://doi.org/10.1016/S0140-6736(10)60061-Xspa
dc.relation.referencesRibeiro, V., Dias, N., Paiva, T., Hagström-Bex, L., Nitz, N., Pratesi, R., & Hecht, M. (2020). Current trends in the pharmacological management of Chagas disease. International Journal for Parasitology: Drugs and Drug Resistance, 12(November 2019), 7–17. https://doi.org/10.1016/j.ijpddr.2019.11.004spa
dc.relation.referencesRomanha, A. J., de Castro, S. L., Soeiro, M. de N. C., Lannes-Vieira, J., Ribeiro, I., Talvani, A., Bourdin, B., Blum, B., Olivieri, B., Zani, C., Spadafora, C., Chiari, E., Chatelain, E., Chaves, G., Calzada, J. E., Bustamante, J. M., Freitas-Junior, L. H., Romero, L. I., Bahia, M. T., … Andrade, Z. de A. (2010). In vitro and in vivo experimental models for drug screening and development for Chagas disease. Memorias Do Instituto Oswaldo Cruz, 105(2), 233–238. https://doi.org/10.1590/S0074-02762010000200022spa
dc.relation.referencesRomero, I., Téllez, J., Romanha, A. J., Steindel, M., & Grisard, E. C. (2015). Upregulation of cysteine synthase and cystathionine β-synthase contributes to Leishmania braziliensis survival under oxidative stress. Antimicrobial Agents and Chemotherapy, 59(8), 4770–4781. https://doi.org/10.1128/AAC.04880-14spa
dc.relation.referencesRomero, I., Téllez, J., Yamanaka, L. E., Steindel, M., Romanha, A. J., & Grisard, E. C. (2014). Transsulfuration is an active pathway for cysteine biosynthesis in Trypanosoma rangeli. Parasites and Vectors, 7(1), 1–11. https://doi.org/10.1186/1756-3305-7-197spa
dc.relation.referencesSalassa, B. N., & Romano, P. S. (2019). Autophagy: A necessary process during the Trypanosoma cruzi life-cycle. Virulence, 10(1), 460–469. https://doi.org/10.1080/21505594.2018.1543517spa
dc.relation.referencesSánchez-Valdéz, F. J., Padilla, A., Wang, W., Orr, D., & Tarleton, R. (2017). Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure. BioRxiv, 1–20. https://doi.org/10.1101/235762spa
dc.relation.referencesSantoro, G. F., Cardoso, M. G., Guimarães, L. G. L., Freire, J. M., & Soares, M. J. (2007). Anti-proliferative effect of the essential oil of Cymbopogon citratus (DC) Stapf (lemongrass) on intracellular amastigotes, bloodstream trypomastigotes and culture epimastigotes of Trypanosoma cruzi (Protozoa: Kinetoplastida). Parasitology, 134(11), 1649–1656. https://doi.org/10.1017/S0031182007002958spa
dc.relation.referencesSantos, E. de S., Silva, D. K. C., Reis, B. P. Z. C. dos, Barreto, B. C., Cardoso, C. M. A., Ribeiro dos Santos, R., Meira, C. S., & Soares, M. B. P. (2021). Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy. Frontiers in Cellular and Infection Microbiology, 11(November), 1–12. https://doi.org/10.3389/fcimb.2021.765879spa
dc.relation.referencesSchnell, R., Sriram, D., & Schneider, G. (2015). Pyridoxal-phosphate dependent mycobacterial cysteine synthases: Structure, mechanism and potential as drug targets. Biochimica et Biophysica Acta - Proteins and Proteomics, 1854(9), 1175–1183. https://doi.org/10.1016/j.bbapap.2014.11.010spa
dc.relation.referencesSchoch, C. L., Ciufo, S., Domrachev, M., Hotton, C. L., Kannan, S., Khovanskaya, R., Leipe, D., Mcveigh, R., O’Neill, K., Robbertse, B., Sharma, S., Soussov, V., Sullivan, J. P., Sun, L., Turner, S., & Karsch-Mizrachi, I. (2020). NCBI Taxonomy: a comprehensive update on curation, resources and tools. Database : The Journal of Biological Databases and Curation, 2020. https://doi.org/10.1093/database/baaa062spa
dc.relation.referencesSereno, D., Holzmuller, P., & Lemesre, J. L. (2000). Efficacy of second line drugs on antimonyl-resistant amastigotes of Leishmania infantum. Acta Tropica, 74(1), 25–31. https://doi.org/10.1016/S0001-706X(99)00048-0spa
dc.relation.referencesSilber, A. M., Tonelli, R. R., Lopes, C. G., Cunha-e-Silva, N., Torrecilhas, A. C. T., Schumacher, R. I., Colli, W., & Alves, M. J. M. (2009). Glucose uptake in the mammalian stages of Trypanosoma cruzi. Molecular and Biochemical Parasitology, 168(1), 102–108. https://doi.org/10.1016/j.molbiopara.2009.07.006spa
dc.relation.referencesSingh, S., Sablok, G., Farmer, R., Singh, A. K., Gautam, B., & Kumar, S. (2013). Molecular dynamic simulation and inhibitor prediction of cysteine synthase structured model as a potential drug target for trichomoniasis. BioMed Research International, 2013. https://doi.org/10.1155/2013/390920spa
dc.relation.referencesSouza, R., Lima, F., Barros, R. M., Cortez, D. R., Santos, M. F., Cordero, E. M., Ruiz, J. C., Goldenberg, S., Teixeira, M. M. G., & da Silveira, J. F. (2011). Genome size, karyotype polymorphism and chromosomal evolution in Trypanosoma cruzi. PLoS ONE, 6(8). https://doi.org/10.1371/journal.pone.0023042spa
dc.relation.referencesSowerby, K., Freitag-Pohl, S., Murillo, A. M., Silber, A. M., & Pohl, E. (2023). Cysteine synthase: multiple structures of a key enzyme in cysteine synthesis and a potential drug target for Chagas disease and leishmaniasis. Acta Crystallographica Section D Structural Biology, 79(6), 518–530. https://doi.org/10.1107/S2059798323003613spa
dc.relation.referencesTakagi, H., & Ohtsu, I. (2016). L -Cysteine Metabolism and Fermentation in Microorganisms. https://doi.org/10.1007/10spa
dc.relation.referencesTeixeira, A., Hecht, M., Guimaro, M., Sousa, A., & Nitz, N. (2011). Pathogenesis of chagas’ disease: Parasite persistence and autoimmunity. Clinical Microbiology Reviews, 24(3), 592–630. https://doi.org/10.1128/CMR.00063-10spa
dc.relation.referencesTeixeira, Benchimol, M., Crepaldi, P. H., & de Souza, W. (2012). Interactive Multimedia to Teach the Life Cycle of Trypanosoma cruzi, the Causative Agent of Chagas Disease. PLoS Neglected Tropical Diseases, 6(8), 1–13. https://doi.org/10.1371/journal.pntd.0001749spa
dc.relation.referencesTéllez, J., Amarillo, A., Suarez, C., Cardozo, C., Guerra, D., Ochoa, R., Muskus, C., & Romero, I. (2022). Prediction of potential cysteine synthase inhibitors of Leishmania braziliensis and Leishmania major parasites by computational screening. Acta Tropica, 225(October 2021). https://doi.org/10.1016/j.actatropica.2021.106182spa
dc.relation.referencesTéllez, J., Romero, I., Romanha, A. J., & Steindel, M. (2019). Drug transporter and oxidative stress gene expression in human macrophages infected with benznidazole-sensitive and naturally benznidazole-resistant Trypanosoma cruzi parasites treated with benznidazole. Parasites and Vectors, 12(1), 1–9. https://doi.org/10.1186/s13071-019-3485-9spa
dc.relation.referencesThomas, D., & Surdin-Kerjan, Y. (1997). Metabolism of sulfur amino acids in Saccharomyces cerevisiae. Microbiology and Molecular Biology Reviews, 61(4), 503–532. https://doi.org/10.1128/mmbr.61.4.503-532.1997spa
dc.relation.referencesTyers, M., & Wright, G. D. (2019). Drug combinations: a strategy to extend the life of antibiotics in the 21st century. Nature Reviews Microbiology, 17(3), 141–155. https://doi.org/10.1038/s41579-018-0141-xspa
dc.relation.referencesTyler, K., & Engman, D. (2001). The life cycle of Trypanosoma cruzi revisited. International Journal for Parasitology, 31(5–6), 472–481. https://doi.org/10.1016/S0020-7519(01)00153-9spa
dc.relation.referencesValencia, L., Muñoz, D. L., Robledo, S. M., Echeverri, F., Arango, G. J., Vélez, I. D., & Triana, O. (2011). Trypanocidal and cytotoxic activity of extracts of Colombian plants. Biomedica, 31(4), 552–559. https://doi.org/10.7705/biomedica.v31i4.426spa
dc.relation.referencesViotti, R., Vigliano, C., Lococo, B., Alvarez, M. G., Petti, M., Bertocchi, G., & Armenti, A. (2009). Side effects of benznidazole as treatment in chronic Chagas disease: Fears and realities. Expert Review of Anti-Infective Therapy, 7(2), 157–163. https://doi.org/10.1586/14787210.7.2.157spa
dc.relation.referencesWang, S. J., Huang, C. F., & Yu, M. L. (2021). Elbasvir and grazoprevir for the treatment of hepatitis C. Expert Review of Anti-Infective Therapy, 19(9), 1071–1081. https://doi.org/10.1080/14787210.2021.1874351spa
dc.relation.referencesWHO, W. H. O. (2015). Chagas disease in Latin America: an epidemiological update based on 2010 estimates. Relevé Épidémiologique Hebdomadaire / Section d’hygiène Du Secrétariat de La Société Des Nations = Weekly Epidemiological Record / Health Section of the Secretariat of the League of Nations, 90(6), 33–43.spa
dc.relation.referencesWHO, W. H. O. (2021). Chagas disease (also known as American trypanosomiasis). 2021. https://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis)#:~:text=secondary thrombotic strokes.-,Treatment,the cases of congenital transmission.spa
dc.relation.referencesWilkinson, S. R., Taylor, M. C., Horn, D., Kelly, J. M., & Cheeseman, I. (2008). A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes. Proceedings of the National Academy of Sciences of the United States of America, 105(13), 5022–5027. https://doi.org/10.1073/pnas.0711014105spa
dc.relation.referencesWilliams, R. A. M., Westrop, G. D., & Coombs, G. H. (2009). Two pathways for cysteine biosynthesis in Leishmania major. Biochemical Journal, 420(3), 451–462. https://doi.org/10.1042/BJ20082441spa
dc.relation.referencesXia, H., Lu, C., Wang, Y., Zaongo, S. D., Hu, Y., Wu, Y., Yan, Z., & Ma, P. (2020). Efficacy and Safety of Direct-Acting Antiviral Therapy in Patients With Chronic Hepatitis C Virus Infection: A Real-World Single-Center Experience in Tianjin, China. Frontiers in Pharmacology, 11(May), 1–8. https://doi.org/10.3389/fphar.2020.00710spa
dc.relation.referencesZingales, B. (2018). Trypanosoma cruzi genetic diversity: Something new for something known about Chagas disease manifestations, serodiagnosis and drug sensitivity. Acta Tropica, 184(April 2017), 38–52. https://doi.org/10.1016/j.actatropica.2017.09.017spa
dc.relation.referencesZingales, Bianca, Miles, M. A., Campbell, D. A., Tibayrenc, M., Macedo, A. M., Teixeira, M. M. G., Schijman, A. G., Llewellyn, M. S., Lages-Silva, E., Machado, C. R., Andrade, S. G., & Sturm, N. R. (2012). The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications. Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases, 12(2), 240–253. https://doi.org/10.1016/j.meegid.2011.12.009spa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseReconocimiento 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/spa
dc.subject.decsParásitosspa
dc.subject.decsParasiteseng
dc.subject.proposalTrypanosoma cruzieng
dc.subject.proposalEnfermedad de Chagasspa
dc.subject.proposalCisteína sintasaspa
dc.subject.proposalEfecto tripanocidaspa
dc.subject.proposalBlanco terapéuticospa
dc.subject.proposalInhibición enzimáticaspa
dc.subject.proposalElbasvir
dc.subject.proposalGlecaprevir
dc.subject.proposalChagas diseaseeng
dc.subject.proposalCysteine synthaseeng
dc.subject.proposalTrypanocidal activityeng
dc.subject.proposalTherapeutic targeteng
dc.subject.proposalEnzyme inhibitioneng
dc.titleEvaluación de la actividad tripanocida de elbasvir y glecaprevir y del efecto sobre la actividad de la enzima Cisteína sintasa de Trypanosoma cruzi in vitrospa
dc.title.translatedEvaluation of the trypanocidal activity of elbasvir and glecaprevir and the effect on the activity of the Trypanosoma cruzi cysteine synthase enzyme in vitroeng
dc.typeTrabajo de grado - Maestríaspa
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oaire.awardtitleIdentificación de compuestos inhibidores de la enzima Cisteína Sintasa de Trypanosoma cruzi con potencial actividad tripanocida para el desarrollo de una terapia selectiva contra este parásitospa
oaire.fundernamePontificia Universidad Javerianaspa

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