Heteroleptic Oxidovanadium(V) Complexes with Activity against Infective and Non-Infective Stages of <i>Trypanosoma cruzi</i>
Five heteroleptic compounds, [V<sup>V</sup>O(IN-2H)(L-H)], where L are 8-hydroxyquinoline derivatives and IN is a Schiff base ligand, were synthesized and characterized in both the solid and solution state. The compounds were evaluated on epimastigotes and trypomastigotes of <i>Try...
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MDPI AG
2021-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/17/5375 |
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| author | Gonzalo Scalese Ignacio Machado Gustavo Salinas Leticia Pérez-Díaz Dinorah Gambino |
| author_facet | Gonzalo Scalese Ignacio Machado Gustavo Salinas Leticia Pérez-Díaz Dinorah Gambino |
| author_sort | Gonzalo Scalese |
| collection | DOAJ |
| description | Five heteroleptic compounds, [V<sup>V</sup>O(IN-2H)(L-H)], where L are 8-hydroxyquinoline derivatives and IN is a Schiff base ligand, were synthesized and characterized in both the solid and solution state. The compounds were evaluated on epimastigotes and trypomastigotes of <i>Trypanosoma cruzi</i> as well as on VERO cells, as a mammalian cell model. Compounds showed activity against trypomastigotes with IC<sub>50</sub> values of 0.29–3.02 μM. IN ligand and the new [V<sup>V</sup>O<sub>2</sub>(IN-H)] complex showed negligible activity. The most active compound [V<sup>V</sup>O(IN-2H)(L2-H)], with L2 = 5-chloro-7-iodo-8-hydroxyquinoline, showed good selectivity towards the parasite and was selected to carry out further biological studies. Stability studies suggested a partial decomposition in solution. [V<sup>V</sup>O(IN-2H)(L2-H)] affects the infection potential of cell-derived trypomastigotes. Low total vanadium uptake by parasites and preferential accumulation in the soluble proteins fraction were determined. A trypanocide effect was observed when incubating epimastigotes with 10 × IC<sub>50</sub> values of [V<sup>V</sup>O(IN-2H)(L2-H)] and the generation of ROS after treatments was suggested. Fluorescence competition measurements with DNA:ethidium bromide adduct showed a moderate DNA interaction of the complexes. In vivo toxicity study on <i>C. elegans</i> model showed no toxicity up to a 100 μM concentration of [V<sup>V</sup>O(IN-2H)(L2-H)]. This compound could be considered a prospective anti-<i>T. cruzi</i> agent that deserves further research. |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T08:05:56Z |
| publishDate | 2021-09-01 |
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| series | Molecules |
| spelling | doaj.art-7051204c8e65470cbc61ba165ec88f2c2023-11-22T11:03:12ZengMDPI AGMolecules1420-30492021-09-012617537510.3390/molecules26175375Heteroleptic Oxidovanadium(V) Complexes with Activity against Infective and Non-Infective Stages of <i>Trypanosoma cruzi</i>Gonzalo Scalese0Ignacio Machado1Gustavo Salinas2Leticia Pérez-Díaz3Dinorah Gambino4Área Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo 11800, UruguayÁrea Química Analítica, Facultad de Química, Universidad de la República, Montevideo 11800, UruguayWorm Biology Lab, Institut Pasteur de Montevideo, Montevideo 11400, UruguayLaboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la República, Montevideo 11400, UruguayÁrea Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo 11800, UruguayFive heteroleptic compounds, [V<sup>V</sup>O(IN-2H)(L-H)], where L are 8-hydroxyquinoline derivatives and IN is a Schiff base ligand, were synthesized and characterized in both the solid and solution state. The compounds were evaluated on epimastigotes and trypomastigotes of <i>Trypanosoma cruzi</i> as well as on VERO cells, as a mammalian cell model. Compounds showed activity against trypomastigotes with IC<sub>50</sub> values of 0.29–3.02 μM. IN ligand and the new [V<sup>V</sup>O<sub>2</sub>(IN-H)] complex showed negligible activity. The most active compound [V<sup>V</sup>O(IN-2H)(L2-H)], with L2 = 5-chloro-7-iodo-8-hydroxyquinoline, showed good selectivity towards the parasite and was selected to carry out further biological studies. Stability studies suggested a partial decomposition in solution. [V<sup>V</sup>O(IN-2H)(L2-H)] affects the infection potential of cell-derived trypomastigotes. Low total vanadium uptake by parasites and preferential accumulation in the soluble proteins fraction were determined. A trypanocide effect was observed when incubating epimastigotes with 10 × IC<sub>50</sub> values of [V<sup>V</sup>O(IN-2H)(L2-H)] and the generation of ROS after treatments was suggested. Fluorescence competition measurements with DNA:ethidium bromide adduct showed a moderate DNA interaction of the complexes. In vivo toxicity study on <i>C. elegans</i> model showed no toxicity up to a 100 μM concentration of [V<sup>V</sup>O(IN-2H)(L2-H)]. This compound could be considered a prospective anti-<i>T. cruzi</i> agent that deserves further research.https://www.mdpi.com/1420-3049/26/17/5375vanadium8-hydroxyquinoline derivatives<i>Trypanosoma cruzi</i>metallomicstrypomastigotes |
| spellingShingle | Gonzalo Scalese Ignacio Machado Gustavo Salinas Leticia Pérez-Díaz Dinorah Gambino Heteroleptic Oxidovanadium(V) Complexes with Activity against Infective and Non-Infective Stages of <i>Trypanosoma cruzi</i> Molecules vanadium 8-hydroxyquinoline derivatives <i>Trypanosoma cruzi</i> metallomics trypomastigotes |
| title | Heteroleptic Oxidovanadium(V) Complexes with Activity against Infective and Non-Infective Stages of <i>Trypanosoma cruzi</i> |
| title_full | Heteroleptic Oxidovanadium(V) Complexes with Activity against Infective and Non-Infective Stages of <i>Trypanosoma cruzi</i> |
| title_fullStr | Heteroleptic Oxidovanadium(V) Complexes with Activity against Infective and Non-Infective Stages of <i>Trypanosoma cruzi</i> |
| title_full_unstemmed | Heteroleptic Oxidovanadium(V) Complexes with Activity against Infective and Non-Infective Stages of <i>Trypanosoma cruzi</i> |
| title_short | Heteroleptic Oxidovanadium(V) Complexes with Activity against Infective and Non-Infective Stages of <i>Trypanosoma cruzi</i> |
| title_sort | heteroleptic oxidovanadium v complexes with activity against infective and non infective stages of i trypanosoma cruzi i |
| topic | vanadium 8-hydroxyquinoline derivatives <i>Trypanosoma cruzi</i> metallomics trypomastigotes |
| url | https://www.mdpi.com/1420-3049/26/17/5375 |
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