Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole

Background: Chagas disease (CD), caused by Trypanosoma cruzi, represents a healththreat to around 20 million people worldwide. Side effects of benznidazole (Bzn)cause 15-20% of patients to discontinue their treatment. Evidence has increased infavour of the use of drug combinations to improve the eff...

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Autores: Ortiz, Javier Esteban, Piñeiro Gomez, Mauricio Daniel, Martines Peinado, Nieves, Barrera, Patricia Andrea, Sosa, Miguel, Bastida, Jaume, Alonso Padilla, Julio, Feresin, Gabriela Egly
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/224977
Acceso en línea:http://hdl.handle.net/11336/224977
Access Level:acceso abierto
Palabra clave:AMARYLLIDACEAE ALKALOIDS
CHAGAS DISEASE
ANTIPARASITIC ASSAYS
NEGLECTED DISEASE
CANDIMINE
TRYPANOSOMA CRUZI
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
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oai_identifier_str oai:ri.conicet.gov.ar:11336/224977
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole
title Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole
spellingShingle Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole
Ortiz, Javier Esteban
AMARYLLIDACEAE ALKALOIDS
CHAGAS DISEASE
ANTIPARASITIC ASSAYS
NEGLECTED DISEASE
CANDIMINE
TRYPANOSOMA CRUZI
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
title_short Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole
title_full Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole
title_fullStr Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole
title_full_unstemmed Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole
title_sort Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole
dc.creator.none.fl_str_mv Ortiz, Javier Esteban
Piñeiro Gomez, Mauricio Daniel
Martines Peinado, Nieves
Barrera, Patricia Andrea
Sosa, Miguel
Bastida, Jaume
Alonso Padilla, Julio
Feresin, Gabriela Egly
author Ortiz, Javier Esteban
author_facet Ortiz, Javier Esteban
Piñeiro Gomez, Mauricio Daniel
Martines Peinado, Nieves
Barrera, Patricia Andrea
Sosa, Miguel
Bastida, Jaume
Alonso Padilla, Julio
Feresin, Gabriela Egly
author_role author
author2 Piñeiro Gomez, Mauricio Daniel
Martines Peinado, Nieves
Barrera, Patricia Andrea
Sosa, Miguel
Bastida, Jaume
Alonso Padilla, Julio
Feresin, Gabriela Egly
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AMARYLLIDACEAE ALKALOIDS
CHAGAS DISEASE
ANTIPARASITIC ASSAYS
NEGLECTED DISEASE
CANDIMINE
TRYPANOSOMA CRUZI
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
topic AMARYLLIDACEAE ALKALOIDS
CHAGAS DISEASE
ANTIPARASITIC ASSAYS
NEGLECTED DISEASE
CANDIMINE
TRYPANOSOMA CRUZI
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
description Background: Chagas disease (CD), caused by Trypanosoma cruzi, represents a healththreat to around 20 million people worldwide. Side effects of benznidazole (Bzn)cause 15-20% of patients to discontinue their treatment. Evidence has increased infavour of the use of drug combinations to improve the efficacy and tolerance of thetreatment. Natural products are well known to provide structures that could serve asnew drugs or scaffolds for CD treatment. Spp of the Amaryllidoideae sub family ofAmaryllidaceae family are known by its bioactives alkaloids, which have a reportedantiparasitic activity.Purpose: To evaluate the anti-T. cruzi activity of the isolated alkaloid candimine(Cnd) from Hippeastrum escoipense Slanis & Huaylla; and to assess the combinationeffect between Cnd and Bzn against different life stages of T. cruzi parasites.Methods: The chemical profile of H. escoipense alkaloids extract (AE-H. escoipense),including quantitation of Cnd was performed through GC/MS and UPLC-MS/MStechniques. Subsequently, Cnd was isolated using Shephadex LH20. Then, the AE-H.escoipense and Cnd were tested against T. cruzi, (epimastigotes, trypomastigotes, andamastigotes) by in vitro proliferation and viability assays. The cytotoxicity wasevaluated against Vero and HepG2 mammalian cells. The ultrastructural analysis wasperform by Transmission Electron Microcopy (TEM) and mitochondrial activity wascarried out by MTT assay. Drug combination assay between Cnd and Bzn wasevaluated using the Chou-Talalay method.4Results: The AE-H. escoipense and Cnd showed high and specific anti-T. cruziactivity, comparable to Bzn. Cnd induces ultrastructural changes in T. cruzi, such asvacuolization, membrane blebs and increases the mitochondrial activity. Regarding,the interaction between Cnd and Bzn generates synergism in the combinations of0.25×IC50 in epimastigotes, 2×IC50 in trypomastigotes+amastigotes, and 0.25, 2, and4×IC50 in amastigotes.Conclusion: The synergism between Cnd and Bzn indicates that the combination atthe concentration of 4×IC50 could be useful as an effective new therapy against CD inthe chronic stage. Thus, Cnd isolated from the leaves of the H. escoipense emerges aspotential candidate for the development of a new drug for the treatment of CD.
publishDate 2023
dc.date.none.fl_str_mv 2023-03
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/11336/224977
Ortiz, Javier Esteban; Piñeiro Gomez, Mauricio Daniel; Martines Peinado, Nieves; Barrera, Patricia Andrea; Sosa, Miguel; et al.; Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole; Elsevier Gmbh; Phytomedicine; 114; 3-2023; 1-30
0944-7113
CONICET Digital
CONICET
url http://hdl.handle.net/11336/224977
identifier_str_mv Ortiz, Javier Esteban; Piñeiro Gomez, Mauricio Daniel; Martines Peinado, Nieves; Barrera, Patricia Andrea; Sosa, Miguel; et al.; Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole; Elsevier Gmbh; Phytomedicine; 114; 3-2023; 1-30
0944-7113
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0944711323001496
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.phymed.2023.154788
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Gmbh
publisher.none.fl_str_mv Elsevier Gmbh
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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
_version_ 1799195167128813568
spelling Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazoleOrtiz, Javier EstebanPiñeiro Gomez, Mauricio DanielMartines Peinado, NievesBarrera, Patricia AndreaSosa, MiguelBastida, JaumeAlonso Padilla, JulioFeresin, Gabriela EglyAMARYLLIDACEAE ALKALOIDSCHAGAS DISEASEANTIPARASITIC ASSAYSNEGLECTED DISEASECANDIMINETRYPANOSOMA CRUZIhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Background: Chagas disease (CD), caused by Trypanosoma cruzi, represents a healththreat to around 20 million people worldwide. Side effects of benznidazole (Bzn)cause 15-20% of patients to discontinue their treatment. Evidence has increased infavour of the use of drug combinations to improve the efficacy and tolerance of thetreatment. Natural products are well known to provide structures that could serve asnew drugs or scaffolds for CD treatment. Spp of the Amaryllidoideae sub family ofAmaryllidaceae family are known by its bioactives alkaloids, which have a reportedantiparasitic activity.Purpose: To evaluate the anti-T. cruzi activity of the isolated alkaloid candimine(Cnd) from Hippeastrum escoipense Slanis & Huaylla; and to assess the combinationeffect between Cnd and Bzn against different life stages of T. cruzi parasites.Methods: The chemical profile of H. escoipense alkaloids extract (AE-H. escoipense),including quantitation of Cnd was performed through GC/MS and UPLC-MS/MStechniques. Subsequently, Cnd was isolated using Shephadex LH20. Then, the AE-H.escoipense and Cnd were tested against T. cruzi, (epimastigotes, trypomastigotes, andamastigotes) by in vitro proliferation and viability assays. The cytotoxicity wasevaluated against Vero and HepG2 mammalian cells. The ultrastructural analysis wasperform by Transmission Electron Microcopy (TEM) and mitochondrial activity wascarried out by MTT assay. Drug combination assay between Cnd and Bzn wasevaluated using the Chou-Talalay method.4Results: The AE-H. escoipense and Cnd showed high and specific anti-T. cruziactivity, comparable to Bzn. Cnd induces ultrastructural changes in T. cruzi, such asvacuolization, membrane blebs and increases the mitochondrial activity. Regarding,the interaction between Cnd and Bzn generates synergism in the combinations of0.25×IC50 in epimastigotes, 2×IC50 in trypomastigotes+amastigotes, and 0.25, 2, and4×IC50 in amastigotes.Conclusion: The synergism between Cnd and Bzn indicates that the combination atthe concentration of 4×IC50 could be useful as an effective new therapy against CD inthe chronic stage. Thus, Cnd isolated from the leaves of the H. escoipense emerges aspotential candidate for the development of a new drug for the treatment of CD.Fil: Ortiz, Javier Esteban. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Piñeiro Gomez, Mauricio Daniel. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Martines Peinado, Nieves. Universidad de Barcelona; EspañaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Sosa, Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Bastida, Jaume. Universidad de Barcelona. Facultad de Farmacia; EspañaFil: Alonso Padilla, Julio. Universidad de Barcelona; EspañaFil: Feresin, Gabriela Egly. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaElsevier Gmbh2023-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/224977Ortiz, Javier Esteban; Piñeiro Gomez, Mauricio Daniel; Martines Peinado, Nieves; Barrera, Patricia Andrea; Sosa, Miguel; et al.; Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole; Elsevier Gmbh; Phytomedicine; 114; 3-2023; 1-300944-7113CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0944711323001496info:eu-repo/semantics/altIdentifier/doi/10.1016/j.phymed.2023.154788info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:45:11Zoai:ri.conicet.gov.ar:11336/224977instacron: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:34982024-05-08 13:45:12.18CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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