In vitro and in vivo effects of digoxin derivatives on promastigotes and amastigotes of Leishmania infantum
Leishmania infantum is responsible for visceral leishmaniasis, the most severe form of the disease. The treatments currently used are pentavalent antimonials and amphotericin B, but they present serious side effects and resistant species that already exist. Therefore, it is necessary to find new com...
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Taibah University for Science |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/16583655.2023.2289240 |
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| author | Gabriellen Menezes Migliani de Castro Yasmin da Silva Fontes Silmara Lúcia Grego Alves Leandro Augusto Oliveira Barbosa José Augusto Ferreira Perez Villar Antonio Galina Filho Sergio Henrique Seabra Anna Lea Silva Barreto Ana Claudia Tessis Dirlei Nico Antonio Ferreira-Pereira |
| author_facet | Gabriellen Menezes Migliani de Castro Yasmin da Silva Fontes Silmara Lúcia Grego Alves Leandro Augusto Oliveira Barbosa José Augusto Ferreira Perez Villar Antonio Galina Filho Sergio Henrique Seabra Anna Lea Silva Barreto Ana Claudia Tessis Dirlei Nico Antonio Ferreira-Pereira |
| author_sort | Gabriellen Menezes Migliani de Castro |
| collection | DOAJ |
| description | Leishmania infantum is responsible for visceral leishmaniasis, the most severe form of the disease. The treatments currently used are pentavalent antimonials and amphotericin B, but they present serious side effects and resistant species that already exist. Therefore, it is necessary to find new compounds to avoid those acute problems. In vitro, this study evaluated the effects of fifteen digoxin derivative compounds on promastigotes and two of these compounds on amastigotes of L. infantum. We also assess the impact of these compounds on mitochondrial metabolism. The results showed that two of the fifteen compounds tested showed a high anti-Leishmania effect. Compounds 3 and 15 showed no toxicity across the cell lines RAW 264.7. Compound 15 inhibited macrophage infection and reduced the number of amastigotes. The two compounds showed a reduction in oxygen consumption by promastigotes. In this way, compounds 3 and 15 appear to be promising anti-leishmanial. Therefore, we checked both compounds in vivo also evaluating the toxicity by measuring ALT, AST, urea, and creatinine. Our results may contribute in the future to the development and application of new anti-Leishmania drugs. |
| format | Article |
| id | doaj-art-173af655ea054b9e8062f82f12a14e4d |
| institution | OA Journals |
| issn | 1658-3655 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Taibah University for Science |
| spelling | doaj-art-173af655ea054b9e8062f82f12a14e4d2025-08-20T01:57:51ZengTaylor & Francis GroupJournal of Taibah University for Science1658-36552024-12-0118110.1080/16583655.2023.2289240In vitro and in vivo effects of digoxin derivatives on promastigotes and amastigotes of Leishmania infantumGabriellen Menezes Migliani de Castro0Yasmin da Silva Fontes1Silmara Lúcia Grego Alves2Leandro Augusto Oliveira Barbosa3José Augusto Ferreira Perez Villar4Antonio Galina Filho5Sergio Henrique Seabra6Anna Lea Silva Barreto7Ana Claudia Tessis8Dirlei Nico9Antonio Ferreira-Pereira10Laboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, IMPG, UFRJ, Rio de Janeiro, BrazilLaboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, IMPG, UFRJ, Rio de Janeiro, BrazilLaboratório de Bioquímica Celular, UFSJ Campus Centro-Oeste Dona Lindu, Divinópolis, BrazilLaboratório de Bioquímica Celular, UFSJ Campus Centro-Oeste Dona Lindu, Divinópolis, BrazilLaboratório de Síntese Orgânica e Nanoestruturas, UFSJ Campus Centro-Oeste Dona Lindu, Divinópolis, BrazilLaboratório de Bioenergética e Fisiologia Mitocondrial, IBqM, UFRJ, Rio de Janeiro, BrazilLaboratório de Tecnologia em Bioquímica e Microscopia, UEZO, Rio de Janeiro, BrazilLaboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, IMPG, UFRJ, Rio de Janeiro, BrazilLaboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, IMPG, UFRJ, Rio de Janeiro, BrazilDepartamento de Microbiologia Geral, IMPG, UFRJ, Rio de Janeiro, BrazilLaboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, IMPG, UFRJ, Rio de Janeiro, BrazilLeishmania infantum is responsible for visceral leishmaniasis, the most severe form of the disease. The treatments currently used are pentavalent antimonials and amphotericin B, but they present serious side effects and resistant species that already exist. Therefore, it is necessary to find new compounds to avoid those acute problems. In vitro, this study evaluated the effects of fifteen digoxin derivative compounds on promastigotes and two of these compounds on amastigotes of L. infantum. We also assess the impact of these compounds on mitochondrial metabolism. The results showed that two of the fifteen compounds tested showed a high anti-Leishmania effect. Compounds 3 and 15 showed no toxicity across the cell lines RAW 264.7. Compound 15 inhibited macrophage infection and reduced the number of amastigotes. The two compounds showed a reduction in oxygen consumption by promastigotes. In this way, compounds 3 and 15 appear to be promising anti-leishmanial. Therefore, we checked both compounds in vivo also evaluating the toxicity by measuring ALT, AST, urea, and creatinine. Our results may contribute in the future to the development and application of new anti-Leishmania drugs.https://www.tandfonline.com/doi/10.1080/16583655.2023.2289240LeishmaniaL. infantumleishmaniasisdigoxindigitalis |
| spellingShingle | Gabriellen Menezes Migliani de Castro Yasmin da Silva Fontes Silmara Lúcia Grego Alves Leandro Augusto Oliveira Barbosa José Augusto Ferreira Perez Villar Antonio Galina Filho Sergio Henrique Seabra Anna Lea Silva Barreto Ana Claudia Tessis Dirlei Nico Antonio Ferreira-Pereira In vitro and in vivo effects of digoxin derivatives on promastigotes and amastigotes of Leishmania infantum Journal of Taibah University for Science Leishmania L. infantum leishmaniasis digoxin digitalis |
| title | In vitro and in vivo effects of digoxin derivatives on promastigotes and amastigotes of Leishmania infantum |
| title_full | In vitro and in vivo effects of digoxin derivatives on promastigotes and amastigotes of Leishmania infantum |
| title_fullStr | In vitro and in vivo effects of digoxin derivatives on promastigotes and amastigotes of Leishmania infantum |
| title_full_unstemmed | In vitro and in vivo effects of digoxin derivatives on promastigotes and amastigotes of Leishmania infantum |
| title_short | In vitro and in vivo effects of digoxin derivatives on promastigotes and amastigotes of Leishmania infantum |
| title_sort | in vitro and in vivo effects of digoxin derivatives on promastigotes and amastigotes of leishmania infantum |
| topic | Leishmania L. infantum leishmaniasis digoxin digitalis |
| url | https://www.tandfonline.com/doi/10.1080/16583655.2023.2289240 |
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