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Synergistic effect and ultrastructural changes in Trypanosoma cruzi caused by isoobtusilactone A in short exposure of time
Butanolides have shown a variety of biological effects including anti-inflammatory, antibacterial, and antiprotozoal effects against certain strains of Trypanosoma cruzi. Considering the lack of an effective drug to treat T. cruzi infections and the prominent results obtained in literature with this...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842926/ https://www.ncbi.nlm.nih.gov/pubmed/33507972 http://dx.doi.org/10.1371/journal.pone.0245882 |
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author | de Almeida, Júlio Menta Nunes, Felipe Oliveira Ceole, Lígia Fernanda Klimeck, Tabata D’Maiella Freitas da Cruz, Letícia Alves Tófoli, Danilo Borges, Beatriz Santana Garcez, Walmir Silva Tozetti, Inês Aparecida Medeiros, Lia Carolina Soares Garcez, Fernanda Rodrigues Ferreira, Alda Maria Teixeira |
author_facet | de Almeida, Júlio Menta Nunes, Felipe Oliveira Ceole, Lígia Fernanda Klimeck, Tabata D’Maiella Freitas da Cruz, Letícia Alves Tófoli, Danilo Borges, Beatriz Santana Garcez, Walmir Silva Tozetti, Inês Aparecida Medeiros, Lia Carolina Soares Garcez, Fernanda Rodrigues Ferreira, Alda Maria Teixeira |
author_sort | de Almeida, Júlio Menta |
collection | PubMed |
description | Butanolides have shown a variety of biological effects including anti-inflammatory, antibacterial, and antiprotozoal effects against certain strains of Trypanosoma cruzi. Considering the lack of an effective drug to treat T. cruzi infections and the prominent results obtained in literature with this class of lactones, we investigated the anti-T. cruzi activity of five butanolides isolated from two species of Lauraceae, Aiouea trinervis and Mezilaurus crassiramea. Initially, the activity of these compounds was evaluated on epimastigote forms of the parasite, after a treatment period of 4 h, followed by testing on amastigotes, trypomastigotes, and mammalian cells. Next, the synergistic effect of active butanolides against amastigotes was evaluated. Further, metacyclogenesis inhibition and infectivity assays were performed for the most active compound, followed by ultrastructural analysis of the treated amastigotes and trypomastigotes. Among the five butanolides studied, majoranolide and isoobtusilactone A were active against all forms of the parasite, with good selectivity indexes in Vero cells. Both butanolides were more active than the control drug against trypomastigote and epimastigote forms and also had a synergic effect on amastigotes. The most active compound, isoobtusilactone A, which showed activity against all tested strains inhibited metacyclogenesis and infection of new host cells. In addition, ultrastructural analysis revealed that this butanolide caused extensive damage to the mitochondria of both amastigotes and trypomastigotes, resulting in severe morphological changes in the infective forms of the parasite. Altogether, our results highlight the potential of butanolides against the etiologic agent of Chagas disease and the relevance of isoobtusilactone A as a strong anti-T. cruzi drug, affecting different events of the life cycle and all evolutionary forms of parasite after a short period of exposure. |
format | Online Article Text |
id | pubmed-7842926 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-78429262021-02-04 Synergistic effect and ultrastructural changes in Trypanosoma cruzi caused by isoobtusilactone A in short exposure of time de Almeida, Júlio Menta Nunes, Felipe Oliveira Ceole, Lígia Fernanda Klimeck, Tabata D’Maiella Freitas da Cruz, Letícia Alves Tófoli, Danilo Borges, Beatriz Santana Garcez, Walmir Silva Tozetti, Inês Aparecida Medeiros, Lia Carolina Soares Garcez, Fernanda Rodrigues Ferreira, Alda Maria Teixeira PLoS One Research Article Butanolides have shown a variety of biological effects including anti-inflammatory, antibacterial, and antiprotozoal effects against certain strains of Trypanosoma cruzi. Considering the lack of an effective drug to treat T. cruzi infections and the prominent results obtained in literature with this class of lactones, we investigated the anti-T. cruzi activity of five butanolides isolated from two species of Lauraceae, Aiouea trinervis and Mezilaurus crassiramea. Initially, the activity of these compounds was evaluated on epimastigote forms of the parasite, after a treatment period of 4 h, followed by testing on amastigotes, trypomastigotes, and mammalian cells. Next, the synergistic effect of active butanolides against amastigotes was evaluated. Further, metacyclogenesis inhibition and infectivity assays were performed for the most active compound, followed by ultrastructural analysis of the treated amastigotes and trypomastigotes. Among the five butanolides studied, majoranolide and isoobtusilactone A were active against all forms of the parasite, with good selectivity indexes in Vero cells. Both butanolides were more active than the control drug against trypomastigote and epimastigote forms and also had a synergic effect on amastigotes. The most active compound, isoobtusilactone A, which showed activity against all tested strains inhibited metacyclogenesis and infection of new host cells. In addition, ultrastructural analysis revealed that this butanolide caused extensive damage to the mitochondria of both amastigotes and trypomastigotes, resulting in severe morphological changes in the infective forms of the parasite. Altogether, our results highlight the potential of butanolides against the etiologic agent of Chagas disease and the relevance of isoobtusilactone A as a strong anti-T. cruzi drug, affecting different events of the life cycle and all evolutionary forms of parasite after a short period of exposure. Public Library of Science 2021-01-28 /pmc/articles/PMC7842926/ /pubmed/33507972 http://dx.doi.org/10.1371/journal.pone.0245882 Text en © 2021 de Almeida et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article de Almeida, Júlio Menta Nunes, Felipe Oliveira Ceole, Lígia Fernanda Klimeck, Tabata D’Maiella Freitas da Cruz, Letícia Alves Tófoli, Danilo Borges, Beatriz Santana Garcez, Walmir Silva Tozetti, Inês Aparecida Medeiros, Lia Carolina Soares Garcez, Fernanda Rodrigues Ferreira, Alda Maria Teixeira Synergistic effect and ultrastructural changes in Trypanosoma cruzi caused by isoobtusilactone A in short exposure of time |
title | Synergistic effect and ultrastructural changes in Trypanosoma cruzi caused by isoobtusilactone A in short exposure of time |
title_full | Synergistic effect and ultrastructural changes in Trypanosoma cruzi caused by isoobtusilactone A in short exposure of time |
title_fullStr | Synergistic effect and ultrastructural changes in Trypanosoma cruzi caused by isoobtusilactone A in short exposure of time |
title_full_unstemmed | Synergistic effect and ultrastructural changes in Trypanosoma cruzi caused by isoobtusilactone A in short exposure of time |
title_short | Synergistic effect and ultrastructural changes in Trypanosoma cruzi caused by isoobtusilactone A in short exposure of time |
title_sort | synergistic effect and ultrastructural changes in trypanosoma cruzi caused by isoobtusilactone a in short exposure of time |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842926/ https://www.ncbi.nlm.nih.gov/pubmed/33507972 http://dx.doi.org/10.1371/journal.pone.0245882 |
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