Venom alkaloids against Chagas disease parasite: search for effective therapies

Autores
Silva, Rafael C. M. Costa; Fox, Eduardo G. P.; Gomes, Fabio M.; Feijó, Daniel F.; Ramos, Isabela; Koeller, Carolina M.; Costa, Tatiana F. R.; Rodrigues, Nathalia S.; Lima, Ana P.; Atella, Georgia C.; Rocha de Miranda, Kildare; Schoijet, Alejandra Cecilia; Alonso, Guillermo Daniel; de Alcântara Machado, Ednildo; Heise, Norton
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas disease is an important disease affecting millions of patients in the New World and is caused by a protozoan transmitted by haematophagous kissing bugs. It can be treated with drugs during the early acute phase; however, effective therapy against the chronic form of Chagas disease has yet to be discovered and developed. We herein tested the activity of solenopsin alkaloids extracted from two species of fire ants against the protozoan parasite Trypanosoma cruzi, the aetiologic agent of Chagas disease. Although IC50 determinations showed that solenopsins are more toxic to the parasite than benznidazole, the drug of choice for Chagas disease treatment, the ant alkaloids presented a lower selectivity index. As a result of exposure to the alkaloids, the parasites became swollen and rounded in shape, with hypertrophied contractile vacuoles and intense cytoplasmic vacuolization, possibly resulting in osmotic stress; no accumulation of multiple kinetoplasts and/or nuclei was detected. Overexpressing phosphatidylinositol 3-kinase—an enzyme essential for osmoregulation that is a known target of solenopsins in mammalian cells—did not prevent swelling and vacuolization, nor did it counteract the toxic effects of alkaloids on the parasites. Additional experimental results suggested that solenopsins induced a type of autophagic and programmed cell death in T. cruzi. Solenopsins also reduced the intracellular proliferation of T. cruzi amastigotes in infected macrophages in a concentration-dependent manner and demonstrated activity against Trypanosoma brucei rhodesiense bloodstream forms, which is another important aetiological kinetoplastid parasite. The results suggest the potential of solenopsins as novel natural drugs against neglected parasitic diseases caused by kinetoplastids.
Fil: Silva, Rafael C. M. Costa. Universidade Federal do Rio de Janeiro; Brasil
Fil: Fox, Eduardo G. P.. Universidade Federal do Rio de Janeiro; Brasil. South China Agricultural University; China
Fil: Gomes, Fabio M.. Universidade Federal do Rio de Janeiro; Brasil. National Institutes of Health; Estados Unidos
Fil: Feijó, Daniel F.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Ramos, Isabela. Universidade Federal do Rio de Janeiro; Brasil
Fil: Koeller, Carolina M.. Universidade Federal do Rio de Janeiro; Brasil. University at Buffalo; Estados Unidos
Fil: Costa, Tatiana F. R.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Rodrigues, Nathalia S.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Lima, Ana P.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Atella, Georgia C.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Rocha de Miranda, Kildare. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem; Brasil
Fil: Schoijet, Alejandra Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: de Alcântara Machado, Ednildo. Universidade Federal do Rio de Janeiro; Brasil
Fil: Heise, Norton. Universidade Federal do Rio de Janeiro; Brasil
Materia
TRYPANOSOMA CRUZI
ALKALOIDS
OSMOTIC STRESS
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:11336/112558
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/112558
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Venom alkaloids against Chagas disease parasite: search for effective therapiesSilva, Rafael C. M. CostaFox, Eduardo G. P.Gomes, Fabio M.Feijó, Daniel F.Ramos, IsabelaKoeller, Carolina M.Costa, Tatiana F. R.Rodrigues, Nathalia S.Lima, Ana P.Atella, Georgia C.Rocha de Miranda, KildareSchoijet, Alejandra CeciliaAlonso, Guillermo Danielde Alcântara Machado, EdnildoHeise, NortonTRYPANOSOMA CRUZIALKALOIDSOSMOTIC STRESShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chagas disease is an important disease affecting millions of patients in the New World and is caused by a protozoan transmitted by haematophagous kissing bugs. It can be treated with drugs during the early acute phase; however, effective therapy against the chronic form of Chagas disease has yet to be discovered and developed. We herein tested the activity of solenopsin alkaloids extracted from two species of fire ants against the protozoan parasite Trypanosoma cruzi, the aetiologic agent of Chagas disease. Although IC50 determinations showed that solenopsins are more toxic to the parasite than benznidazole, the drug of choice for Chagas disease treatment, the ant alkaloids presented a lower selectivity index. As a result of exposure to the alkaloids, the parasites became swollen and rounded in shape, with hypertrophied contractile vacuoles and intense cytoplasmic vacuolization, possibly resulting in osmotic stress; no accumulation of multiple kinetoplasts and/or nuclei was detected. Overexpressing phosphatidylinositol 3-kinase—an enzyme essential for osmoregulation that is a known target of solenopsins in mammalian cells—did not prevent swelling and vacuolization, nor did it counteract the toxic effects of alkaloids on the parasites. Additional experimental results suggested that solenopsins induced a type of autophagic and programmed cell death in T. cruzi. Solenopsins also reduced the intracellular proliferation of T. cruzi amastigotes in infected macrophages in a concentration-dependent manner and demonstrated activity against Trypanosoma brucei rhodesiense bloodstream forms, which is another important aetiological kinetoplastid parasite. The results suggest the potential of solenopsins as novel natural drugs against neglected parasitic diseases caused by kinetoplastids.Fil: Silva, Rafael C. M. Costa. Universidade Federal do Rio de Janeiro; BrasilFil: Fox, Eduardo G. P.. Universidade Federal do Rio de Janeiro; Brasil. South China Agricultural University; ChinaFil: Gomes, Fabio M.. Universidade Federal do Rio de Janeiro; Brasil. National Institutes of Health; Estados UnidosFil: Feijó, Daniel F.. Universidade Federal do Rio de Janeiro; BrasilFil: Ramos, Isabela. Universidade Federal do Rio de Janeiro; BrasilFil: Koeller, Carolina M.. Universidade Federal do Rio de Janeiro; Brasil. University at Buffalo; Estados UnidosFil: Costa, Tatiana F. R.. Universidade Federal do Rio de Janeiro; BrasilFil: Rodrigues, Nathalia S.. Universidade Federal do Rio de Janeiro; BrasilFil: Lima, Ana P.. Universidade Federal do Rio de Janeiro; BrasilFil: Atella, Georgia C.. Universidade Federal do Rio de Janeiro; BrasilFil: Rocha de Miranda, Kildare. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem; BrasilFil: Schoijet, Alejandra Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: de Alcântara Machado, Ednildo. Universidade Federal do Rio de Janeiro; BrasilFil: Heise, Norton. Universidade Federal do Rio de Janeiro; BrasilNature Research2020-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/112558Silva, Rafael C. M. Costa; Fox, Eduardo G. P.; Gomes, Fabio M.; Feijó, Daniel F.; Ramos, Isabela; et al.; Venom alkaloids against Chagas disease parasite: search for effective therapies; Nature Research; Scientific Reports; 10; 10642; 6-2020; 1-162045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-020-67324-8info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-020-67324-8info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:27:02Zoai:ri.conicet.gov.ar:11336/112558instacron: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:34982025-10-22 11:27:03.006CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Venom alkaloids against Chagas disease parasite: search for effective therapies
title Venom alkaloids against Chagas disease parasite: search for effective therapies
spellingShingle Venom alkaloids against Chagas disease parasite: search for effective therapies
Silva, Rafael C. M. Costa
TRYPANOSOMA CRUZI
ALKALOIDS
OSMOTIC STRESS
title_short Venom alkaloids against Chagas disease parasite: search for effective therapies
title_full Venom alkaloids against Chagas disease parasite: search for effective therapies
title_fullStr Venom alkaloids against Chagas disease parasite: search for effective therapies
title_full_unstemmed Venom alkaloids against Chagas disease parasite: search for effective therapies
title_sort Venom alkaloids against Chagas disease parasite: search for effective therapies
dc.creator.none.fl_str_mv Silva, Rafael C. M. Costa
Fox, Eduardo G. P.
Gomes, Fabio M.
Feijó, Daniel F.
Ramos, Isabela
Koeller, Carolina M.
Costa, Tatiana F. R.
Rodrigues, Nathalia S.
Lima, Ana P.
Atella, Georgia C.
Rocha de Miranda, Kildare
Schoijet, Alejandra Cecilia
Alonso, Guillermo Daniel
de Alcântara Machado, Ednildo
Heise, Norton
author Silva, Rafael C. M. Costa
author_facet Silva, Rafael C. M. Costa
Fox, Eduardo G. P.
Gomes, Fabio M.
Feijó, Daniel F.
Ramos, Isabela
Koeller, Carolina M.
Costa, Tatiana F. R.
Rodrigues, Nathalia S.
Lima, Ana P.
Atella, Georgia C.
Rocha de Miranda, Kildare
Schoijet, Alejandra Cecilia
Alonso, Guillermo Daniel
de Alcântara Machado, Ednildo
Heise, Norton
author_role author
author2 Fox, Eduardo G. P.
Gomes, Fabio M.
Feijó, Daniel F.
Ramos, Isabela
Koeller, Carolina M.
Costa, Tatiana F. R.
Rodrigues, Nathalia S.
Lima, Ana P.
Atella, Georgia C.
Rocha de Miranda, Kildare
Schoijet, Alejandra Cecilia
Alonso, Guillermo Daniel
de Alcântara Machado, Ednildo
Heise, Norton
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TRYPANOSOMA CRUZI
ALKALOIDS
OSMOTIC STRESS
topic TRYPANOSOMA CRUZI
ALKALOIDS
OSMOTIC STRESS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chagas disease is an important disease affecting millions of patients in the New World and is caused by a protozoan transmitted by haematophagous kissing bugs. It can be treated with drugs during the early acute phase; however, effective therapy against the chronic form of Chagas disease has yet to be discovered and developed. We herein tested the activity of solenopsin alkaloids extracted from two species of fire ants against the protozoan parasite Trypanosoma cruzi, the aetiologic agent of Chagas disease. Although IC50 determinations showed that solenopsins are more toxic to the parasite than benznidazole, the drug of choice for Chagas disease treatment, the ant alkaloids presented a lower selectivity index. As a result of exposure to the alkaloids, the parasites became swollen and rounded in shape, with hypertrophied contractile vacuoles and intense cytoplasmic vacuolization, possibly resulting in osmotic stress; no accumulation of multiple kinetoplasts and/or nuclei was detected. Overexpressing phosphatidylinositol 3-kinase—an enzyme essential for osmoregulation that is a known target of solenopsins in mammalian cells—did not prevent swelling and vacuolization, nor did it counteract the toxic effects of alkaloids on the parasites. Additional experimental results suggested that solenopsins induced a type of autophagic and programmed cell death in T. cruzi. Solenopsins also reduced the intracellular proliferation of T. cruzi amastigotes in infected macrophages in a concentration-dependent manner and demonstrated activity against Trypanosoma brucei rhodesiense bloodstream forms, which is another important aetiological kinetoplastid parasite. The results suggest the potential of solenopsins as novel natural drugs against neglected parasitic diseases caused by kinetoplastids.
Fil: Silva, Rafael C. M. Costa. Universidade Federal do Rio de Janeiro; Brasil
Fil: Fox, Eduardo G. P.. Universidade Federal do Rio de Janeiro; Brasil. South China Agricultural University; China
Fil: Gomes, Fabio M.. Universidade Federal do Rio de Janeiro; Brasil. National Institutes of Health; Estados Unidos
Fil: Feijó, Daniel F.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Ramos, Isabela. Universidade Federal do Rio de Janeiro; Brasil
Fil: Koeller, Carolina M.. Universidade Federal do Rio de Janeiro; Brasil. University at Buffalo; Estados Unidos
Fil: Costa, Tatiana F. R.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Rodrigues, Nathalia S.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Lima, Ana P.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Atella, Georgia C.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Rocha de Miranda, Kildare. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem; Brasil
Fil: Schoijet, Alejandra Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: de Alcântara Machado, Ednildo. Universidade Federal do Rio de Janeiro; Brasil
Fil: Heise, Norton. Universidade Federal do Rio de Janeiro; Brasil
description Chagas disease is an important disease affecting millions of patients in the New World and is caused by a protozoan transmitted by haematophagous kissing bugs. It can be treated with drugs during the early acute phase; however, effective therapy against the chronic form of Chagas disease has yet to be discovered and developed. We herein tested the activity of solenopsin alkaloids extracted from two species of fire ants against the protozoan parasite Trypanosoma cruzi, the aetiologic agent of Chagas disease. Although IC50 determinations showed that solenopsins are more toxic to the parasite than benznidazole, the drug of choice for Chagas disease treatment, the ant alkaloids presented a lower selectivity index. As a result of exposure to the alkaloids, the parasites became swollen and rounded in shape, with hypertrophied contractile vacuoles and intense cytoplasmic vacuolization, possibly resulting in osmotic stress; no accumulation of multiple kinetoplasts and/or nuclei was detected. Overexpressing phosphatidylinositol 3-kinase—an enzyme essential for osmoregulation that is a known target of solenopsins in mammalian cells—did not prevent swelling and vacuolization, nor did it counteract the toxic effects of alkaloids on the parasites. Additional experimental results suggested that solenopsins induced a type of autophagic and programmed cell death in T. cruzi. Solenopsins also reduced the intracellular proliferation of T. cruzi amastigotes in infected macrophages in a concentration-dependent manner and demonstrated activity against Trypanosoma brucei rhodesiense bloodstream forms, which is another important aetiological kinetoplastid parasite. The results suggest the potential of solenopsins as novel natural drugs against neglected parasitic diseases caused by kinetoplastids.
publishDate 2020
dc.date.none.fl_str_mv 2020-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/112558
Silva, Rafael C. M. Costa; Fox, Eduardo G. P.; Gomes, Fabio M.; Feijó, Daniel F.; Ramos, Isabela; et al.; Venom alkaloids against Chagas disease parasite: search for effective therapies; Nature Research; Scientific Reports; 10; 10642; 6-2020; 1-16
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/112558
identifier_str_mv Silva, Rafael C. M. Costa; Fox, Eduardo G. P.; Gomes, Fabio M.; Feijó, Daniel F.; Ramos, Isabela; et al.; Venom alkaloids against Chagas disease parasite: search for effective therapies; Nature Research; Scientific Reports; 10; 10642; 6-2020; 1-16
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-020-67324-8
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-020-67324-8
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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