Trypanocidal Activity of Four Sesquiterpene Lactones Isolated from Asteraceae Species
The sesquiterpene lactones eupatoriopicrin, estafietin, eupahakonenin B and minimolide have been isolated from Argentinean Astearaceae species and have been found to be active against <i>Trypanosoma cruzi</i> epimastigotes. The aim of this work was to evaluate the activity of these compo...
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MDPI AG
2020-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/9/2014 |
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| author | Orlando G. Elso Augusto E. Bivona Andrés Sanchez Alberti Natacha Cerny Lucas Fabian Celina Morales César A. N. Catalán Emilio L. Malchiodi Silvia I. Cazorla Valeria P. Sülsen |
| author_facet | Orlando G. Elso Augusto E. Bivona Andrés Sanchez Alberti Natacha Cerny Lucas Fabian Celina Morales César A. N. Catalán Emilio L. Malchiodi Silvia I. Cazorla Valeria P. Sülsen |
| author_sort | Orlando G. Elso |
| collection | DOAJ |
| description | The sesquiterpene lactones eupatoriopicrin, estafietin, eupahakonenin B and minimolide have been isolated from Argentinean Astearaceae species and have been found to be active against <i>Trypanosoma cruzi</i> epimastigotes. The aim of this work was to evaluate the activity of these compounds by analyzing their effect against the stages of the parasites that are infective for the human. Even more interesting, we aimed to determine the effect of the most active and selective compound on an <i>in vivo</i> model of <i>T. cruzi</i> infection. Eupatoriopicrin was the most active against amastigotes and tripomastigotes (IC<sub>50</sub> = 2.3 µg/mL, and 7.2 µg/mL, respectively) and displayed a high selectivity index. This compound was selected to study on an <i>in vivo</i> model of <i>T. cruzi</i> infection. The administration of 1 mg/kg/day of eupatoriopicrin for five consecutive days to infected mice produced a significant reduction in the parasitaemia levels in comparison with non-treated animals (area under parasitaemia curves 4.48 vs. 30.47, respectively). Skeletal muscular tissues from eupatopicrin-treated mice displayed only focal and interstitial lymphocyte inflammatory infiltrates and small areas of necrotic; by contrast, skeletal tissues from <i>T. cruzi</i> infected mice treated with the vehicle showed severe lymphocyte inflammatory infiltrates with necrosis of the adjacent myocytes. The results indicate that eupatoriopicrin could be considered a promising candidate for the development of new therapeutic agents for Chagas disease. |
| first_indexed | 2024-03-10T20:13:40Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T20:13:40Z |
| publishDate | 2020-04-01 |
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| series | Molecules |
| spelling | doaj.art-65fe52f1e4944dd3a1bbd3ddf385caf12023-11-19T22:43:35ZengMDPI AGMolecules1420-30492020-04-01259201410.3390/molecules25092014Trypanocidal Activity of Four Sesquiterpene Lactones Isolated from Asteraceae SpeciesOrlando G. Elso0Augusto E. Bivona1Andrés Sanchez Alberti2Natacha Cerny3Lucas Fabian4Celina Morales5César A. N. Catalán6Emilio L. Malchiodi7Silvia I. Cazorla8Valeria P. Sülsen9Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), CONICET–Universidad de Buenos Aires, Junín 956 2° floor, Buenos Aires 1113, ArgentinaCátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 4° floor, Buenos Aires 1113, ArgentinaCátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 4° floor, Buenos Aires 1113, ArgentinaInstituto de Ecología y Desarrollo Sustentable (INEDES), CONICET—Universidad Nacional de Luján, Ruta 5 y Avenida Constitución, Luján 6700, ArgentinaInstituto de Química y Metabolismo del Fármaco (IQUIMEFA), CONICET–Universidad de Buenos Aires, Junín 956 2° floor, Buenos Aires 1113, ArgentinaDepartamento de Patología, Instituto de Fisiopatología Cardiovascular, Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires 1113, ArgentinaInstituto de Química del Noroeste—CONICET (INQUINOA), CONICET—Universidad Nacional de Tucumán, Ayacucho 471, San Miguel de Tucumán T4000INI, ArgentinaCátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 4° floor, Buenos Aires 1113, ArgentinaInstituto de Microbiología y Parasitología Médica—CONICET (IMPaM), Facultad de Medicina, CONICET—Universidad de Buenos Aires, Paraguay 2155. 13° floor, Buenos Aires C1121ABG, ArgentinaInstituto de Química y Metabolismo del Fármaco (IQUIMEFA), CONICET–Universidad de Buenos Aires, Junín 956 2° floor, Buenos Aires 1113, ArgentinaThe sesquiterpene lactones eupatoriopicrin, estafietin, eupahakonenin B and minimolide have been isolated from Argentinean Astearaceae species and have been found to be active against <i>Trypanosoma cruzi</i> epimastigotes. The aim of this work was to evaluate the activity of these compounds by analyzing their effect against the stages of the parasites that are infective for the human. Even more interesting, we aimed to determine the effect of the most active and selective compound on an <i>in vivo</i> model of <i>T. cruzi</i> infection. Eupatoriopicrin was the most active against amastigotes and tripomastigotes (IC<sub>50</sub> = 2.3 µg/mL, and 7.2 µg/mL, respectively) and displayed a high selectivity index. This compound was selected to study on an <i>in vivo</i> model of <i>T. cruzi</i> infection. The administration of 1 mg/kg/day of eupatoriopicrin for five consecutive days to infected mice produced a significant reduction in the parasitaemia levels in comparison with non-treated animals (area under parasitaemia curves 4.48 vs. 30.47, respectively). Skeletal muscular tissues from eupatopicrin-treated mice displayed only focal and interstitial lymphocyte inflammatory infiltrates and small areas of necrotic; by contrast, skeletal tissues from <i>T. cruzi</i> infected mice treated with the vehicle showed severe lymphocyte inflammatory infiltrates with necrosis of the adjacent myocytes. The results indicate that eupatoriopicrin could be considered a promising candidate for the development of new therapeutic agents for Chagas disease.https://www.mdpi.com/1420-3049/25/9/2014<i>Trypanosoma cruzi</i>sesquiterpene lactonesAsteraceae<i>Stevia</i> spp.<i>Mikania</i> spp. |
| spellingShingle | Orlando G. Elso Augusto E. Bivona Andrés Sanchez Alberti Natacha Cerny Lucas Fabian Celina Morales César A. N. Catalán Emilio L. Malchiodi Silvia I. Cazorla Valeria P. Sülsen Trypanocidal Activity of Four Sesquiterpene Lactones Isolated from Asteraceae Species Molecules <i>Trypanosoma cruzi</i> sesquiterpene lactones Asteraceae <i>Stevia</i> spp. <i>Mikania</i> spp. |
| title | Trypanocidal Activity of Four Sesquiterpene Lactones Isolated from Asteraceae Species |
| title_full | Trypanocidal Activity of Four Sesquiterpene Lactones Isolated from Asteraceae Species |
| title_fullStr | Trypanocidal Activity of Four Sesquiterpene Lactones Isolated from Asteraceae Species |
| title_full_unstemmed | Trypanocidal Activity of Four Sesquiterpene Lactones Isolated from Asteraceae Species |
| title_short | Trypanocidal Activity of Four Sesquiterpene Lactones Isolated from Asteraceae Species |
| title_sort | trypanocidal activity of four sesquiterpene lactones isolated from asteraceae species |
| topic | <i>Trypanosoma cruzi</i> sesquiterpene lactones Asteraceae <i>Stevia</i> spp. <i>Mikania</i> spp. |
| url | https://www.mdpi.com/1420-3049/25/9/2014 |
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