Anti-<i>Trypanosoma cruzi</i> Properties of Sesquiterpene Lactones Isolated from <i>Stevia</i> spp.: In Vitro and In Silico Studies
<i>Stevia</i> species (Asteraceae) have been a rich source of terpenoid compounds, mainly sesquiterpene lactones, several of which show antiprotozoal activity. In the search for new trypanocidal compounds, <i>S. satureiifolia</i> var. <i>satureiifolia</i> and <...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/2/647 |
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| author | Jimena Borgo Orlando G. Elso Jessica Gomez Mauro Coll Cesar A. N. Catalán Juan Mucci Guzmán Alvarez Lía M. Randall Patricia Barrera Emilio L. Malchiodi Augusto E. Bivona María Florencia Martini Valeria P. Sülsen |
| author_facet | Jimena Borgo Orlando G. Elso Jessica Gomez Mauro Coll Cesar A. N. Catalán Juan Mucci Guzmán Alvarez Lía M. Randall Patricia Barrera Emilio L. Malchiodi Augusto E. Bivona María Florencia Martini Valeria P. Sülsen |
| author_sort | Jimena Borgo |
| collection | DOAJ |
| description | <i>Stevia</i> species (Asteraceae) have been a rich source of terpenoid compounds, mainly sesquiterpene lactones, several of which show antiprotozoal activity. In the search for new trypanocidal compounds, <i>S. satureiifolia</i> var. <i>satureiifolia</i> and <i>S. alpina</i> were studied. Two sesquiterpene lactones, santhemoidin C and 2-oxo-8-deoxyligustrin, respectively, were isolated. These compounds were assessed in vitro against <i>Trypanosoma cruzi</i> stages, showing IC<sub>50</sub> values of 11.80 and 4.98 on epimastigotes, 56.08 and 26.19 on trypomastigotes and 4.88 and 20.20 µM on amastigotes, respectively. Cytotoxicity was evaluated on Vero cells by the MTT assay. The effect of the compounds on trypanothyone reductase (TcTR), <i>Trans</i>-sialidase (TcTS) and the prolyl oligopeptidase of 80 kDa (Tc80) as potential molecular targets of <i>T. cruzi</i> was investigated. Santhemoidin C inhibited oligopeptidase activity when tested against recombinant Tc80 using a fluorometric assay, reaching an IC<sub>50</sub> of 34.9 µM. Molecular docking was performed to study the interaction between santhemoidin C and the Tc80 protein, reaching high docking energy levels. Plasma membrane shedding and cytoplasmic vacuoles, resembling autophagosomes, were detected by transmission microscopy in parasites treated with santhemoidin C. Based on these results, santhemoidin C represents a promising candidate for further studies in the search for new molecules for the development of trypanocidal drugs. |
| first_indexed | 2024-03-11T08:17:02Z |
| format | Article |
| id | doaj.art-7f501a003c8248bcb73415679501227a |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T08:17:02Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7f501a003c8248bcb73415679501227a2023-11-16T22:42:44ZengMDPI AGPharmaceutics1999-49232023-02-0115264710.3390/pharmaceutics15020647Anti-<i>Trypanosoma cruzi</i> Properties of Sesquiterpene Lactones Isolated from <i>Stevia</i> spp.: In Vitro and In Silico StudiesJimena Borgo0Orlando G. Elso1Jessica Gomez2Mauro Coll3Cesar A. N. Catalán4Juan Mucci5Guzmán Alvarez6Lía M. Randall7Patricia Barrera8Emilio L. Malchiodi9Augusto E. Bivona10María Florencia Martini11Valeria P. Sülsen12Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), CONICET-Universidad de Buenos Aires, Junín 956, piso 2, Buenos Aires C1113AAD, ArgentinaCátedra de Farmacognosia, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, piso 2, Buenos Aires C1113AAD, ArgentinaFacultad de Ciencias Médicas, Instituto de Histología y Embriología “Dr. Mario H. Burgos” (IHEM), Universidad Nacional de Cuyo-CONICET, CC 56, Mendoza 5500, ArgentinaFacultad de Ciencias Médicas, Instituto de Histología y Embriología “Dr. Mario H. Burgos” (IHEM), Universidad Nacional de Cuyo-CONICET, CC 56, Mendoza 5500, ArgentinaInstituto de Química Orgánica, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Ayacucho 471, San Miguel de Tucumán, Tucumán T4000INI, ArgentinaInstituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín-CONICET, Buenos Aires 5500, ArgentinaLaboratorio de Moléculas Bioactivas, Departamento de Ciencias Biológicas, CENUR Litoral Norte, Universidad de la República, Paysandú 60000, UruguayLaboratorio de Moléculas Bioactivas, Departamento de Ciencias Biológicas, CENUR Litoral Norte, Universidad de la República, Paysandú 60000, UruguayFacultad de Ciencias Médicas, Instituto de Histología y Embriología “Dr. Mario H. Burgos” (IHEM), Universidad Nacional de Cuyo-CONICET, CC 56, Mendoza 5500, ArgentinaCátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, piso 4, Buenos Aires C1113AAD, ArgentinaCátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, piso 4, Buenos Aires C1113AAD, ArgentinaInstituto de Química y Metabolismo del Fármaco (IQUIMEFA), CONICET-Universidad de Buenos Aires, Junín 956, piso 2, Buenos Aires C1113AAD, ArgentinaInstituto de Química y Metabolismo del Fármaco (IQUIMEFA), CONICET-Universidad de Buenos Aires, Junín 956, piso 2, Buenos Aires C1113AAD, Argentina<i>Stevia</i> species (Asteraceae) have been a rich source of terpenoid compounds, mainly sesquiterpene lactones, several of which show antiprotozoal activity. In the search for new trypanocidal compounds, <i>S. satureiifolia</i> var. <i>satureiifolia</i> and <i>S. alpina</i> were studied. Two sesquiterpene lactones, santhemoidin C and 2-oxo-8-deoxyligustrin, respectively, were isolated. These compounds were assessed in vitro against <i>Trypanosoma cruzi</i> stages, showing IC<sub>50</sub> values of 11.80 and 4.98 on epimastigotes, 56.08 and 26.19 on trypomastigotes and 4.88 and 20.20 µM on amastigotes, respectively. Cytotoxicity was evaluated on Vero cells by the MTT assay. The effect of the compounds on trypanothyone reductase (TcTR), <i>Trans</i>-sialidase (TcTS) and the prolyl oligopeptidase of 80 kDa (Tc80) as potential molecular targets of <i>T. cruzi</i> was investigated. Santhemoidin C inhibited oligopeptidase activity when tested against recombinant Tc80 using a fluorometric assay, reaching an IC<sub>50</sub> of 34.9 µM. Molecular docking was performed to study the interaction between santhemoidin C and the Tc80 protein, reaching high docking energy levels. Plasma membrane shedding and cytoplasmic vacuoles, resembling autophagosomes, were detected by transmission microscopy in parasites treated with santhemoidin C. Based on these results, santhemoidin C represents a promising candidate for further studies in the search for new molecules for the development of trypanocidal drugs.https://www.mdpi.com/1999-4923/15/2/647sesquiterpene lactones<i>Stevia satureiifolia</i> var <i>satureiifolia</i><i>Stevia alpina</i>santhemoidin C2-oxo-8-deoxyligustrintrypanocidal activity |
| spellingShingle | Jimena Borgo Orlando G. Elso Jessica Gomez Mauro Coll Cesar A. N. Catalán Juan Mucci Guzmán Alvarez Lía M. Randall Patricia Barrera Emilio L. Malchiodi Augusto E. Bivona María Florencia Martini Valeria P. Sülsen Anti-<i>Trypanosoma cruzi</i> Properties of Sesquiterpene Lactones Isolated from <i>Stevia</i> spp.: In Vitro and In Silico Studies Pharmaceutics sesquiterpene lactones <i>Stevia satureiifolia</i> var <i>satureiifolia</i> <i>Stevia alpina</i> santhemoidin C 2-oxo-8-deoxyligustrin trypanocidal activity |
| title | Anti-<i>Trypanosoma cruzi</i> Properties of Sesquiterpene Lactones Isolated from <i>Stevia</i> spp.: In Vitro and In Silico Studies |
| title_full | Anti-<i>Trypanosoma cruzi</i> Properties of Sesquiterpene Lactones Isolated from <i>Stevia</i> spp.: In Vitro and In Silico Studies |
| title_fullStr | Anti-<i>Trypanosoma cruzi</i> Properties of Sesquiterpene Lactones Isolated from <i>Stevia</i> spp.: In Vitro and In Silico Studies |
| title_full_unstemmed | Anti-<i>Trypanosoma cruzi</i> Properties of Sesquiterpene Lactones Isolated from <i>Stevia</i> spp.: In Vitro and In Silico Studies |
| title_short | Anti-<i>Trypanosoma cruzi</i> Properties of Sesquiterpene Lactones Isolated from <i>Stevia</i> spp.: In Vitro and In Silico Studies |
| title_sort | anti i trypanosoma cruzi i properties of sesquiterpene lactones isolated from i stevia i spp in vitro and in silico studies |
| topic | sesquiterpene lactones <i>Stevia satureiifolia</i> var <i>satureiifolia</i> <i>Stevia alpina</i> santhemoidin C 2-oxo-8-deoxyligustrin trypanocidal activity |
| url | https://www.mdpi.com/1999-4923/15/2/647 |
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