Naftifine-analogues as anti-Trypanosoma cruzi agents

Autores
Gerpe, Alejandra; Boiani Santurio, Lucia; Hernández, Paola; Sortino, Maximiliano Andrés; Zacchino, Susana; González, Mercedes; Cerecetto, Hugo
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas disease represents a relevant health problem in Central and South America. The first line of treatment is Nifurtimox and Benznidazole which have a great deal of disadvantages that demands the rapid generation of therapeutic alternatives. Based in our research on aza-thiaheterocycles as anti-Trypanosoma cruzi agents we identified pharmacophores that act through oxidative stress. Here, we describe the synthesis and the activity of new containing bioactive-heterocycles analogues of naftifine as potential T. cruzi membrane sterol biosynthesis inhibitors. Benzimidazole 1,3-dioxides (11 and 13) and quinoxaline 1,4-dioxides (22 and 23) displayed excellent parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated with the compounds showed that any of them are able to accumulate squalene suggesting that in the anti-T. cruzi mechanism of action is not involved the inhibition of sterol biosynthesis. Some derivatives were also tested as antifungal agents. The results obtained in the present work open potential therapeutic possibilities of new compounds for these infectious diseases.
Fil: Gerpe, Alejandra. Universidad de la República; Uruguay
Fil: Boiani Santurio, Lucia. Universidad de la República; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Hernández, Paola. Universidad de la República; Uruguay
Fil: Sortino, Maximiliano Andrés. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Zacchino, Susana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; Argentina
Fil: González, Mercedes. Universidad de la República; Uruguay
Fil: Cerecetto, Hugo. Universidad de la República; Uruguay
Materia
Alkenylamine
Indazole N-Oxide
Benzofuroxan
Benzimidazole 1,3-Dioxide
Quinoxaline 1,4-Dioxide
Anti-T. Cruzi Agents
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/14562
Acceder
id CONICETDig_4ceab1b04ca5908f3459d0e50cc16c25
oai_identifier_str oai:ri.conicet.gov.ar:11336/14562
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Naftifine-analogues as anti-Trypanosoma cruzi agentsGerpe, AlejandraBoiani Santurio, LuciaHernández, PaolaSortino, Maximiliano AndrésZacchino, SusanaGonzález, MercedesCerecetto, HugoAlkenylamineIndazole N-OxideBenzofuroxanBenzimidazole 1,3-DioxideQuinoxaline 1,4-DioxideAnti-T. Cruzi Agentshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Chagas disease represents a relevant health problem in Central and South America. The first line of treatment is Nifurtimox and Benznidazole which have a great deal of disadvantages that demands the rapid generation of therapeutic alternatives. Based in our research on aza-thiaheterocycles as anti-Trypanosoma cruzi agents we identified pharmacophores that act through oxidative stress. Here, we describe the synthesis and the activity of new containing bioactive-heterocycles analogues of naftifine as potential T. cruzi membrane sterol biosynthesis inhibitors. Benzimidazole 1,3-dioxides (11 and 13) and quinoxaline 1,4-dioxides (22 and 23) displayed excellent parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated with the compounds showed that any of them are able to accumulate squalene suggesting that in the anti-T. cruzi mechanism of action is not involved the inhibition of sterol biosynthesis. Some derivatives were also tested as antifungal agents. The results obtained in the present work open potential therapeutic possibilities of new compounds for these infectious diseases.Fil: Gerpe, Alejandra. Universidad de la República; UruguayFil: Boiani Santurio, Lucia. Universidad de la República; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hernández, Paola. Universidad de la República; UruguayFil: Sortino, Maximiliano Andrés. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zacchino, Susana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; ArgentinaFil: González, Mercedes. Universidad de la República; UruguayFil: Cerecetto, Hugo. Universidad de la República; UruguayElsevier Masson2010-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/14562Gerpe, Alejandra; Boiani Santurio, Lucia; Hernández, Paola; Sortino, Maximiliano Andrés; Zacchino, Susana; et al.; Naftifine-analogues as anti-Trypanosoma cruzi agents; Elsevier Masson; European Journal of Medical Chemistry; 45; 6; 6-2010; 2154-21640223-5234enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0223523410000978info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmech.2010.01.052info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:58:44Zoai:ri.conicet.gov.ar:11336/14562instacron: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 09:58:45.015CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Naftifine-analogues as anti-Trypanosoma cruzi agents
title Naftifine-analogues as anti-Trypanosoma cruzi agents
spellingShingle Naftifine-analogues as anti-Trypanosoma cruzi agents
Gerpe, Alejandra
Alkenylamine
Indazole N-Oxide
Benzofuroxan
Benzimidazole 1,3-Dioxide
Quinoxaline 1,4-Dioxide
Anti-T. Cruzi Agents
title_short Naftifine-analogues as anti-Trypanosoma cruzi agents
title_full Naftifine-analogues as anti-Trypanosoma cruzi agents
title_fullStr Naftifine-analogues as anti-Trypanosoma cruzi agents
title_full_unstemmed Naftifine-analogues as anti-Trypanosoma cruzi agents
title_sort Naftifine-analogues as anti-Trypanosoma cruzi agents
dc.creator.none.fl_str_mv Gerpe, Alejandra
Boiani Santurio, Lucia
Hernández, Paola
Sortino, Maximiliano Andrés
Zacchino, Susana
González, Mercedes
Cerecetto, Hugo
author Gerpe, Alejandra
author_facet Gerpe, Alejandra
Boiani Santurio, Lucia
Hernández, Paola
Sortino, Maximiliano Andrés
Zacchino, Susana
González, Mercedes
Cerecetto, Hugo
author_role author
author2 Boiani Santurio, Lucia
Hernández, Paola
Sortino, Maximiliano Andrés
Zacchino, Susana
González, Mercedes
Cerecetto, Hugo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Alkenylamine
Indazole N-Oxide
Benzofuroxan
Benzimidazole 1,3-Dioxide
Quinoxaline 1,4-Dioxide
Anti-T. Cruzi Agents
topic Alkenylamine
Indazole N-Oxide
Benzofuroxan
Benzimidazole 1,3-Dioxide
Quinoxaline 1,4-Dioxide
Anti-T. Cruzi Agents
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chagas disease represents a relevant health problem in Central and South America. The first line of treatment is Nifurtimox and Benznidazole which have a great deal of disadvantages that demands the rapid generation of therapeutic alternatives. Based in our research on aza-thiaheterocycles as anti-Trypanosoma cruzi agents we identified pharmacophores that act through oxidative stress. Here, we describe the synthesis and the activity of new containing bioactive-heterocycles analogues of naftifine as potential T. cruzi membrane sterol biosynthesis inhibitors. Benzimidazole 1,3-dioxides (11 and 13) and quinoxaline 1,4-dioxides (22 and 23) displayed excellent parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated with the compounds showed that any of them are able to accumulate squalene suggesting that in the anti-T. cruzi mechanism of action is not involved the inhibition of sterol biosynthesis. Some derivatives were also tested as antifungal agents. The results obtained in the present work open potential therapeutic possibilities of new compounds for these infectious diseases.
Fil: Gerpe, Alejandra. Universidad de la República; Uruguay
Fil: Boiani Santurio, Lucia. Universidad de la República; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Hernández, Paola. Universidad de la República; Uruguay
Fil: Sortino, Maximiliano Andrés. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Zacchino, Susana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; Argentina
Fil: González, Mercedes. Universidad de la República; Uruguay
Fil: Cerecetto, Hugo. Universidad de la República; Uruguay
description Chagas disease represents a relevant health problem in Central and South America. The first line of treatment is Nifurtimox and Benznidazole which have a great deal of disadvantages that demands the rapid generation of therapeutic alternatives. Based in our research on aza-thiaheterocycles as anti-Trypanosoma cruzi agents we identified pharmacophores that act through oxidative stress. Here, we describe the synthesis and the activity of new containing bioactive-heterocycles analogues of naftifine as potential T. cruzi membrane sterol biosynthesis inhibitors. Benzimidazole 1,3-dioxides (11 and 13) and quinoxaline 1,4-dioxides (22 and 23) displayed excellent parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated with the compounds showed that any of them are able to accumulate squalene suggesting that in the anti-T. cruzi mechanism of action is not involved the inhibition of sterol biosynthesis. Some derivatives were also tested as antifungal agents. The results obtained in the present work open potential therapeutic possibilities of new compounds for these infectious diseases.
publishDate 2010
dc.date.none.fl_str_mv 2010-06
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/11336/14562
Gerpe, Alejandra; Boiani Santurio, Lucia; Hernández, Paola; Sortino, Maximiliano Andrés; Zacchino, Susana; et al.; Naftifine-analogues as anti-Trypanosoma cruzi agents; Elsevier Masson; European Journal of Medical Chemistry; 45; 6; 6-2010; 2154-2164
0223-5234
url http://hdl.handle.net/11336/14562
identifier_str_mv Gerpe, Alejandra; Boiani Santurio, Lucia; Hernández, Paola; Sortino, Maximiliano Andrés; Zacchino, Susana; et al.; Naftifine-analogues as anti-Trypanosoma cruzi agents; Elsevier Masson; European Journal of Medical Chemistry; 45; 6; 6-2010; 2154-2164
0223-5234
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0223523410000978
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmech.2010.01.052
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Masson
publisher.none.fl_str_mv Elsevier Masson
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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score 13.070432

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