High throughput approaches to unravel the mechanism of action of a new vanadium-based compound against Trypanosoma cruzi

Mosquillo, María Florencia - Smircich, Pablo - Lima, Analía - Gehrke, S.A. - Scalese, Gonzalo - Machado, Ignacio - Gambino, Dinorah - Garat, Beatriz - Pérez-Díaz, Leticia

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.


Detalles Bibliográficos
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.
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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
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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