High throughput approaches to unravel the mechanism of action of a new vanadium-based compound against Trypanosoma cruzi
Editor(es): Keramidas, A.
Resumen:
Treatment for Chagas disease, a parasitosis caused by Trypanosoma cruzi, has always been based on two drugs, nifurtimox and benznidazole, despite the toxic side effects described after prolonged prescription. In this work, we study a new prospective antitrypanosomal drug based on vanadium, here named VIVO(5Brsal)(aminophen). We found a good IC50 value, (3.76 ± 0.08) μM, on CL Brener epimastigotes. 1e analysis of cell death mechanism allowed us to rule out the implication of a mechanism based on early apoptosis or necrosis. Recovery assays revealed a trypanostatic effect, accompanied by cell shape and motility alterations. An uptake mostly associated with the insoluble fraction of the parasites was deduced through vanadium determinations. Concordantly, no drastic changes of the parasite transcriptome were detected after 6 h of treatment. Instead, proteomic analysis uncovered the modulation of proteins involved in different processes such as energy and redox metabolism, transport systems, detoxifying pathways, ribosomal protein synthesis, and proteasome protein degradation. Overall, the results here presented lead us to propose that VIVO(5Brsal)(aminophen) exerts a trypanostatic effect on T. cruzi affecting parasite insoluble proteins.
2020 | |
Inglés | |
Universidad de la República | |
COLIBRI | |
https://hdl.handle.net/20.500.12008/31676 | |
Acceso abierto | |
Licencia Creative Commons Atribución (CC - By 4.0) |
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---|---|
author | Mosquillo, María Florencia |
author2 | Smircich, Pablo Lima, Analía Gehrke, S.A. Scalese, Gonzalo Machado, Ignacio Gambino, Dinorah Garat, Beatriz Pérez-Díaz, Leticia |
author2_role | author author author author author author author author |
author_facet | Mosquillo, María Florencia Smircich, Pablo Lima, Analía Gehrke, S.A. Scalese, Gonzalo Machado, Ignacio Gambino, Dinorah Garat, Beatriz Pérez-Díaz, Leticia |
author_role | author |
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collection | COLIBRI |
dc.contributor.filiacion.none.fl_str_mv | Mosquillo María Florencia, Universidad de la República (Uruguay). Facultad de Ciencias. Smircich Pablo, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología. Lima Analía, Institut Pasteur (Uruguay) Gehrke S.A. Scalese Gonzalo, Universidad de la República (Uruguay). Facultad de Química. Machado Ignacio, Universidad de la República (Uruguay). Facultad de Química. Gambino Dinorah, Universidad de la República (Uruguay). Facultad de Química. Garat Beatriz, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología. Pérez-Díaz Leticia, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica. |
dc.creator.editor.none.fl_str_mv | Keramidas, A. |
dc.creator.none.fl_str_mv | Mosquillo, María Florencia Smircich, Pablo Lima, Analía Gehrke, S.A. Scalese, Gonzalo Machado, Ignacio Gambino, Dinorah Garat, Beatriz Pérez-Díaz, Leticia |
dc.date.accessioned.none.fl_str_mv | 2022-05-26T12:42:03Z |
dc.date.available.none.fl_str_mv | 2022-05-26T12:42:03Z |
dc.date.issued.none.fl_str_mv | 2020 |
dc.description.abstract.none.fl_txt_mv | Treatment for Chagas disease, a parasitosis caused by Trypanosoma cruzi, has always been based on two drugs, nifurtimox and benznidazole, despite the toxic side effects described after prolonged prescription. In this work, we study a new prospective antitrypanosomal drug based on vanadium, here named VIVO(5Brsal)(aminophen). We found a good IC50 value, (3.76 ± 0.08) μM, on CL Brener epimastigotes. 1e analysis of cell death mechanism allowed us to rule out the implication of a mechanism based on early apoptosis or necrosis. Recovery assays revealed a trypanostatic effect, accompanied by cell shape and motility alterations. An uptake mostly associated with the insoluble fraction of the parasites was deduced through vanadium determinations. Concordantly, no drastic changes of the parasite transcriptome were detected after 6 h of treatment. Instead, proteomic analysis uncovered the modulation of proteins involved in different processes such as energy and redox metabolism, transport systems, detoxifying pathways, ribosomal protein synthesis, and proteasome protein degradation. Overall, the results here presented lead us to propose that VIVO(5Brsal)(aminophen) exerts a trypanostatic effect on T. cruzi affecting parasite insoluble proteins. |
dc.format.extent.es.fl_str_mv | 10 h. |
dc.format.mimetype.es.fl_str_mv | application/pdf |
dc.identifier.citation.es.fl_str_mv | Mosquillo, M, Smircich, P, Lima, A, [y otros] "High throughput approaches to unravel the mechanism of action of a new vanadium-based compound against Trypanosoma cruzi". Bioinorganic Chemistry and Applications. [en línea] 2020: 1634270. 10 h. DOI: 10.1155/2020/1634270 |
dc.identifier.doi.none.fl_str_mv | 10.1155/2020/1634270 |
dc.identifier.issn.none.fl_str_mv | 1687-479X |
dc.identifier.uri.none.fl_str_mv | https://hdl.handle.net/20.500.12008/31676 |
dc.language.iso.none.fl_str_mv | en eng |
dc.publisher.es.fl_str_mv | Hindawi |
dc.relation.ispartof.es.fl_str_mv | Bioinorganic Chemistry and Applications, 2020: 1634270 |
dc.rights.license.none.fl_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
dc.rights.none.fl_str_mv | info:eu-repo/semantics/openAccess |
dc.source.none.fl_str_mv | reponame:COLIBRI instname:Universidad de la República instacron:Universidad de la República |
dc.title.none.fl_str_mv | High throughput approaches to unravel the mechanism of action of a new vanadium-based compound against Trypanosoma cruzi |
dc.type.es.fl_str_mv | Artículo |
dc.type.none.fl_str_mv | info:eu-repo/semantics/article |
dc.type.version.none.fl_str_mv | info:eu-repo/semantics/publishedVersion |
description | Treatment for Chagas disease, a parasitosis caused by Trypanosoma cruzi, has always been based on two drugs, nifurtimox and benznidazole, despite the toxic side effects described after prolonged prescription. In this work, we study a new prospective antitrypanosomal drug based on vanadium, here named VIVO(5Brsal)(aminophen). We found a good IC50 value, (3.76 ± 0.08) μM, on CL Brener epimastigotes. 1e analysis of cell death mechanism allowed us to rule out the implication of a mechanism based on early apoptosis or necrosis. Recovery assays revealed a trypanostatic effect, accompanied by cell shape and motility alterations. An uptake mostly associated with the insoluble fraction of the parasites was deduced through vanadium determinations. Concordantly, no drastic changes of the parasite transcriptome were detected after 6 h of treatment. Instead, proteomic analysis uncovered the modulation of proteins involved in different processes such as energy and redox metabolism, transport systems, detoxifying pathways, ribosomal protein synthesis, and proteasome protein degradation. Overall, the results here presented lead us to propose that VIVO(5Brsal)(aminophen) exerts a trypanostatic effect on T. cruzi affecting parasite insoluble proteins. |
eu_rights_str_mv | openAccess |
format | article |
id | COLIBRI_23075ee779ee6857b40e176be80727b9 |
identifier_str_mv | Mosquillo, M, Smircich, P, Lima, A, [y otros] "High throughput approaches to unravel the mechanism of action of a new vanadium-based compound against Trypanosoma cruzi". Bioinorganic Chemistry and Applications. [en línea] 2020: 1634270. 10 h. DOI: 10.1155/2020/1634270 1687-479X 10.1155/2020/1634270 |
instacron_str | Universidad de la República |
institution | Universidad de la República |
instname_str | Universidad de la República |
language | eng |
language_invalid_str_mv | en |
network_acronym_str | COLIBRI |
network_name_str | COLIBRI |
oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/31676 |
publishDate | 2020 |
reponame_str | COLIBRI |
repository.mail.fl_str_mv | mabel.seroubian@seciu.edu.uy |
repository.name.fl_str_mv | COLIBRI - Universidad de la República |
repository_id_str | 4771 |
rights_invalid_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
spelling | Mosquillo María Florencia, Universidad de la República (Uruguay). Facultad de Ciencias.Smircich Pablo, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.Lima Analía, Institut Pasteur (Uruguay)Gehrke S.A.Scalese Gonzalo, Universidad de la República (Uruguay). Facultad de Química.Machado Ignacio, Universidad de la República (Uruguay). Facultad de Química.Gambino Dinorah, Universidad de la República (Uruguay). Facultad de Química.Garat Beatriz, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.Pérez-Díaz Leticia, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica.2022-05-26T12:42:03Z2022-05-26T12:42:03Z2020Mosquillo, M, Smircich, P, Lima, A, [y otros] "High throughput approaches to unravel the mechanism of action of a new vanadium-based compound against Trypanosoma cruzi". Bioinorganic Chemistry and Applications. [en línea] 2020: 1634270. 10 h. DOI: 10.1155/2020/16342701687-479Xhttps://hdl.handle.net/20.500.12008/3167610.1155/2020/1634270Treatment for Chagas disease, a parasitosis caused by Trypanosoma cruzi, has always been based on two drugs, nifurtimox and benznidazole, despite the toxic side effects described after prolonged prescription. In this work, we study a new prospective antitrypanosomal drug based on vanadium, here named VIVO(5Brsal)(aminophen). We found a good IC50 value, (3.76 ± 0.08) μM, on CL Brener epimastigotes. 1e analysis of cell death mechanism allowed us to rule out the implication of a mechanism based on early apoptosis or necrosis. Recovery assays revealed a trypanostatic effect, accompanied by cell shape and motility alterations. An uptake mostly associated with the insoluble fraction of the parasites was deduced through vanadium determinations. Concordantly, no drastic changes of the parasite transcriptome were detected after 6 h of treatment. Instead, proteomic analysis uncovered the modulation of proteins involved in different processes such as energy and redox metabolism, transport systems, detoxifying pathways, ribosomal protein synthesis, and proteasome protein degradation. Overall, the results here presented lead us to propose that VIVO(5Brsal)(aminophen) exerts a trypanostatic effect on T. cruzi affecting parasite insoluble proteins.Submitted by Verdun Juan Pablo (jverdun@fcien.edu.uy) on 2022-05-24T22:45:36Z No. of bitstreams: 2 license_rdf: 19875 bytes, checksum: 9fdbed07f52437945402c4e70fa4773e (MD5) 10.115520201634270.pdf: 1584506 bytes, checksum: 033a4aac5650c93bef7abb50b25cb306 (MD5)Approved for entry into archive by Faget Cecilia (lfaget@fcien.edu.uy) on 2022-05-26T12:31:58Z (GMT) No. of bitstreams: 2 license_rdf: 19875 bytes, checksum: 9fdbed07f52437945402c4e70fa4773e (MD5) 10.115520201634270.pdf: 1584506 bytes, checksum: 033a4aac5650c93bef7abb50b25cb306 (MD5)Made available in DSpace by Luna Fabiana (fabiana.luna@seciu.edu.uy) on 2022-05-26T12:42:03Z (GMT). No. of bitstreams: 2 license_rdf: 19875 bytes, checksum: 9fdbed07f52437945402c4e70fa4773e (MD5) 10.115520201634270.pdf: 1584506 bytes, checksum: 033a4aac5650c93bef7abb50b25cb306 (MD5) Previous issue date: 202010 h.application/pdfenengHindawiBioinorganic Chemistry and Applications, 2020: 1634270Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. 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- Universidad de la Repúblicafalse |
spellingShingle | High throughput approaches to unravel the mechanism of action of a new vanadium-based compound against Trypanosoma cruzi Mosquillo, María Florencia |
status_str | publishedVersion |
title | High throughput approaches to unravel the mechanism of action of a new vanadium-based compound against Trypanosoma cruzi |
title_full | High throughput approaches to unravel the mechanism of action of a new vanadium-based compound against Trypanosoma cruzi |
title_fullStr | High throughput approaches to unravel the mechanism of action of a new vanadium-based compound against Trypanosoma cruzi |
title_full_unstemmed | High throughput approaches to unravel the mechanism of action of a new vanadium-based compound against Trypanosoma cruzi |
title_short | High throughput approaches to unravel the mechanism of action of a new vanadium-based compound against Trypanosoma cruzi |
title_sort | High throughput approaches to unravel the mechanism of action of a new vanadium-based compound against Trypanosoma cruzi |
url | https://hdl.handle.net/20.500.12008/31676 |