High Throughput Approaches to Unravel the Mechanism of Action of a New Vanadium-Based Compound against Trypanosoma cruzi
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 name...
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| Format: | Article |
| Language: | English |
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2020-01-01
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| Series: | Bioinorganic Chemistry and Applications |
| Online Access: | http://dx.doi.org/10.1155/2020/1634270 |
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| author | M. Florencia Mosquillo Pablo Smircich Analía Lima Sergio A. Gehrke Gonzalo Scalese Ignacio Machado Dinorah Gambino Beatriz Garat Leticia Pérez-Díaz |
| author_facet | M. Florencia Mosquillo Pablo Smircich Analía Lima Sergio A. Gehrke Gonzalo Scalese Ignacio Machado Dinorah Gambino Beatriz Garat Leticia Pérez-Díaz |
| author_sort | M. Florencia Mosquillo |
| collection | DOAJ |
| 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. The 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. |
| format | Article |
| id | doaj-art-3b3f6848583b4f748ee4976a8fbf20e2 |
| institution | Kabale University |
| issn | 1565-3633 1687-479X |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioinorganic Chemistry and Applications |
| spelling | doaj-art-3b3f6848583b4f748ee4976a8fbf20e22025-02-03T01:04:37ZengWileyBioinorganic Chemistry and Applications1565-36331687-479X2020-01-01202010.1155/2020/16342701634270High Throughput Approaches to Unravel the Mechanism of Action of a New Vanadium-Based Compound against Trypanosoma cruziM. Florencia Mosquillo0Pablo Smircich1Analía Lima2Sergio A. Gehrke3Gonzalo Scalese4Ignacio Machado5Dinorah Gambino6Beatriz Garat7Leticia Pérez-Díaz8Laboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la República, Montevideo, UruguayLaboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la República, Montevideo, UruguayUnidad de Bioquímica y Proteómica Analíticas, Institut Pasteur de Montevideo, Montevideo, UruguayBiotecnos, Technology and Science, Montevideo, UruguayÁrea Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo, UruguayÁrea Química Analítica, Facultad de Química, Universidad de la República, Montevideo, UruguayÁrea Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo, UruguayLaboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la República, Montevideo, UruguayLaboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la República, Montevideo, UruguayTreatment 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. The 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.http://dx.doi.org/10.1155/2020/1634270 |
| spellingShingle | M. Florencia Mosquillo Pablo Smircich Analía Lima Sergio A. Gehrke Gonzalo Scalese Ignacio Machado Dinorah Gambino Beatriz Garat Leticia Pérez-Díaz High Throughput Approaches to Unravel the Mechanism of Action of a New Vanadium-Based Compound against Trypanosoma cruzi Bioinorganic Chemistry and Applications |
| 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 | http://dx.doi.org/10.1155/2020/1634270 |
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