A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycle

Autores
Gomez, Jessica Daniela; Guarise, C.; Cifuente, Diego Alberto; Sosa, Claudia Marcela; Barrera, Patricia Andrea
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Trypanosoma cruzi is a parasite causing Chagas disease, which is endemic in Latin America, but in the last 20 years, it has expanded worldwide. The current treatment is restricted to Nifurtimox and Benznidazole, but both are relatively toxic and have limited efficacy on the patients. The development of new effective therapeutic agents is urgently needed. The sesquiterpene lactones (STLs) are natural compounds purified from native plants of Argentina with multiple pharmacological applications. The STL dehydroleucodine (DhL), has an alpha-methylene group that could react with multiple sulfhydryl group-containing proteins, affecting cellular functions such as proliferation, the activity mitochondrial, leading to the cell death/apoptosis. This study is focused on elucidating the action mechanisms of DhL and its derivative DC-X11, obtained by chemical substitution, on T. cruzi epimastigotes (strain Dm28c). We observed that DhL and DC-X11 have antiproliferative and cytostatic effects on the parasites. By morphological and ultrastructural studies, we observed an increase of parasites with multiple cell nuclei, kinetoplasts, or flagella after the treatment with DC-X11, suggesting an effect on late steps of the cell cycle (i.e., cellular division). These results were confirmed with parasites synchronized with hydroxyurea (HU 20 mM) for 24 h, and then they were treated with the compound. We concluded that the derivative DC-X11 inhibits T. cruzi proliferation by delaying the progression of the cell division. Further studies are necessary to identify the molecular targets affected by DC-X11.
Fil: Gomez, Jessica Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Guarise, C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina
Fil: Cifuente, Diego Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina
Fil: Sosa, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
XXXVII Reunión Científica Anual de la Sociedad de Biología de Cuyo
San Luis
Argentina
Sociedad Biología de Cuyo
Materia
TRYPANOSOMA CRUZI
CELL CYCLE
SEMI-SYNTHETIC MOLECULE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/215984
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/215984
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycleGomez, Jessica DanielaGuarise, C.Cifuente, Diego AlbertoSosa, Claudia MarcelaBarrera, Patricia AndreaTRYPANOSOMA CRUZICELL CYCLESEMI-SYNTHETIC MOLECULEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Trypanosoma cruzi is a parasite causing Chagas disease, which is endemic in Latin America, but in the last 20 years, it has expanded worldwide. The current treatment is restricted to Nifurtimox and Benznidazole, but both are relatively toxic and have limited efficacy on the patients. The development of new effective therapeutic agents is urgently needed. The sesquiterpene lactones (STLs) are natural compounds purified from native plants of Argentina with multiple pharmacological applications. The STL dehydroleucodine (DhL), has an alpha-methylene group that could react with multiple sulfhydryl group-containing proteins, affecting cellular functions such as proliferation, the activity mitochondrial, leading to the cell death/apoptosis. This study is focused on elucidating the action mechanisms of DhL and its derivative DC-X11, obtained by chemical substitution, on T. cruzi epimastigotes (strain Dm28c). We observed that DhL and DC-X11 have antiproliferative and cytostatic effects on the parasites. By morphological and ultrastructural studies, we observed an increase of parasites with multiple cell nuclei, kinetoplasts, or flagella after the treatment with DC-X11, suggesting an effect on late steps of the cell cycle (i.e., cellular division). These results were confirmed with parasites synchronized with hydroxyurea (HU 20 mM) for 24 h, and then they were treated with the compound. We concluded that the derivative DC-X11 inhibits T. cruzi proliferation by delaying the progression of the cell division. Further studies are necessary to identify the molecular targets affected by DC-X11.Fil: Gomez, Jessica Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Guarise, C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Cifuente, Diego Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaXXXVII Reunión Científica Anual de la Sociedad de Biología de CuyoSan LuisArgentinaSociedad Biología de CuyoTech Science Press2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/215984A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycle; XXXVII Reunión Científica Anual de la Sociedad de Biología de Cuyo; San Luis; Argentina; 2019; 14-140327-9545CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://sbcuyo.org.ar/wp-content/uploads/2019/12/Libro-BIOCELL-2019.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:42:43Zoai:ri.conicet.gov.ar:11336/215984instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:42:43.561CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycle
title A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycle
spellingShingle A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycle
Gomez, Jessica Daniela
TRYPANOSOMA CRUZI
CELL CYCLE
SEMI-SYNTHETIC MOLECULE
title_short A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycle
title_full A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycle
title_fullStr A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycle
title_full_unstemmed A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycle
title_sort A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycle
dc.creator.none.fl_str_mv Gomez, Jessica Daniela
Guarise, C.
Cifuente, Diego Alberto
Sosa, Claudia Marcela
Barrera, Patricia Andrea
author Gomez, Jessica Daniela
author_facet Gomez, Jessica Daniela
Guarise, C.
Cifuente, Diego Alberto
Sosa, Claudia Marcela
Barrera, Patricia Andrea
author_role author
author2 Guarise, C.
Cifuente, Diego Alberto
Sosa, Claudia Marcela
Barrera, Patricia Andrea
author2_role author
author
author
author
dc.subject.none.fl_str_mv TRYPANOSOMA CRUZI
CELL CYCLE
SEMI-SYNTHETIC MOLECULE
topic TRYPANOSOMA CRUZI
CELL CYCLE
SEMI-SYNTHETIC MOLECULE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Trypanosoma cruzi is a parasite causing Chagas disease, which is endemic in Latin America, but in the last 20 years, it has expanded worldwide. The current treatment is restricted to Nifurtimox and Benznidazole, but both are relatively toxic and have limited efficacy on the patients. The development of new effective therapeutic agents is urgently needed. The sesquiterpene lactones (STLs) are natural compounds purified from native plants of Argentina with multiple pharmacological applications. The STL dehydroleucodine (DhL), has an alpha-methylene group that could react with multiple sulfhydryl group-containing proteins, affecting cellular functions such as proliferation, the activity mitochondrial, leading to the cell death/apoptosis. This study is focused on elucidating the action mechanisms of DhL and its derivative DC-X11, obtained by chemical substitution, on T. cruzi epimastigotes (strain Dm28c). We observed that DhL and DC-X11 have antiproliferative and cytostatic effects on the parasites. By morphological and ultrastructural studies, we observed an increase of parasites with multiple cell nuclei, kinetoplasts, or flagella after the treatment with DC-X11, suggesting an effect on late steps of the cell cycle (i.e., cellular division). These results were confirmed with parasites synchronized with hydroxyurea (HU 20 mM) for 24 h, and then they were treated with the compound. We concluded that the derivative DC-X11 inhibits T. cruzi proliferation by delaying the progression of the cell division. Further studies are necessary to identify the molecular targets affected by DC-X11.
Fil: Gomez, Jessica Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Guarise, C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina
Fil: Cifuente, Diego Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina
Fil: Sosa, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
XXXVII Reunión Científica Anual de la Sociedad de Biología de Cuyo
San Luis
Argentina
Sociedad Biología de Cuyo
description Trypanosoma cruzi is a parasite causing Chagas disease, which is endemic in Latin America, but in the last 20 years, it has expanded worldwide. The current treatment is restricted to Nifurtimox and Benznidazole, but both are relatively toxic and have limited efficacy on the patients. The development of new effective therapeutic agents is urgently needed. The sesquiterpene lactones (STLs) are natural compounds purified from native plants of Argentina with multiple pharmacological applications. The STL dehydroleucodine (DhL), has an alpha-methylene group that could react with multiple sulfhydryl group-containing proteins, affecting cellular functions such as proliferation, the activity mitochondrial, leading to the cell death/apoptosis. This study is focused on elucidating the action mechanisms of DhL and its derivative DC-X11, obtained by chemical substitution, on T. cruzi epimastigotes (strain Dm28c). We observed that DhL and DC-X11 have antiproliferative and cytostatic effects on the parasites. By morphological and ultrastructural studies, we observed an increase of parasites with multiple cell nuclei, kinetoplasts, or flagella after the treatment with DC-X11, suggesting an effect on late steps of the cell cycle (i.e., cellular division). These results were confirmed with parasites synchronized with hydroxyurea (HU 20 mM) for 24 h, and then they were treated with the compound. We concluded that the derivative DC-X11 inhibits T. cruzi proliferation by delaying the progression of the cell division. Further studies are necessary to identify the molecular targets affected by DC-X11.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/215984
A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycle; XXXVII Reunión Científica Anual de la Sociedad de Biología de Cuyo; San Luis; Argentina; 2019; 14-14
0327-9545
CONICET Digital
CONICET
url http://hdl.handle.net/11336/215984
identifier_str_mv A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycle; XXXVII Reunión Científica Anual de la Sociedad de Biología de Cuyo; San Luis; Argentina; 2019; 14-14
0327-9545
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Tech Science Press
publisher.none.fl_str_mv Tech Science Press
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