5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene

Autores
Gerpe, Alejandra; Alvarez, Guzmán; Benítez, Diego; Boiani, Lucía; Quiroga, Martín; Hernández, Paola; Sortino, Maximiliano Andrés; Zacchino, Susana Alicia Stella; González, Mercedes; Cerecetto, Hugo
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas disease represents a serious public health problem in South America. The first line of treatment is Nifurtimox and Benznidazole which generate toxic effects in treated patients. We have recently shown that a number of 5-nitrofuranes possess activity against Trypanosoma cruzi through oxidative stress and inhibition of parasite ergosterol biosynthesis, specifically at the level of squalene epoxidase. Here, we identify new 5-nitrofuranes and the thia-analogues with excellent effects on the viability of T. cruzi and adequate parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated, during 120 h, with the compounds showed that some of them accumulated squalene suggesting the squalene epoxidase activity inhibition of the parasite. Nifurtimox was able to accumulate squalene only at lower incubation times. Due to this fact some derivatives were also tested as antifungal agents. Quantitative structure-activity relationship studies were also performed showing relevant features for further new derivatives design. Taken together, the results obtained in the present work point to a more general effect of 5-nitrofuranes and 5-nitrothiophenes in trypanosomatids, opening potential therapeutic possibilities of them for these infectious diseases.
Fil: Gerpe, Alejandra. Universidad de la República; Uruguay
Fil: Alvarez, Guzmán. Universidad de la República; Uruguay
Fil: Benítez, Diego. Universidad de la República; Uruguay
Fil: Boiani, Lucía. Universidad de la República; Uruguay
Fil: Quiroga, Martín. No especifíca;
Fil: Hernández, Paola. Universidad de la República; Uruguay
Fil: Sortino, Maximiliano Andrés. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: González, Mercedes. Universidad de la República; Uruguay
Fil: Cerecetto, Hugo. Universidad de la República; Uruguay
Materia
5-NITROTHIOPHENE
8-NITROFURAN
ANTI-TRYPANOSOMA CRUZI COMPOUNDS
SQUALENE EPOXIDASE
STEROL BIOSYNTHESIS INHIBITORS
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:11336/130232
Acceder
id CONICETDig_1cdec4e59168f0cbee150fa167653bcb
oai_identifier_str oai:ri.conicet.gov.ar:11336/130232
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squaleneGerpe, AlejandraAlvarez, GuzmánBenítez, DiegoBoiani, LucíaQuiroga, MartínHernández, PaolaSortino, Maximiliano AndrésZacchino, Susana Alicia StellaGonzález, MercedesCerecetto, Hugo5-NITROTHIOPHENE8-NITROFURANANTI-TRYPANOSOMA CRUZI COMPOUNDSSQUALENE EPOXIDASESTEROL BIOSYNTHESIS INHIBITORShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Chagas disease represents a serious public health problem in South America. The first line of treatment is Nifurtimox and Benznidazole which generate toxic effects in treated patients. We have recently shown that a number of 5-nitrofuranes possess activity against Trypanosoma cruzi through oxidative stress and inhibition of parasite ergosterol biosynthesis, specifically at the level of squalene epoxidase. Here, we identify new 5-nitrofuranes and the thia-analogues with excellent effects on the viability of T. cruzi and adequate parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated, during 120 h, with the compounds showed that some of them accumulated squalene suggesting the squalene epoxidase activity inhibition of the parasite. Nifurtimox was able to accumulate squalene only at lower incubation times. Due to this fact some derivatives were also tested as antifungal agents. Quantitative structure-activity relationship studies were also performed showing relevant features for further new derivatives design. Taken together, the results obtained in the present work point to a more general effect of 5-nitrofuranes and 5-nitrothiophenes in trypanosomatids, opening potential therapeutic possibilities of them for these infectious diseases.Fil: Gerpe, Alejandra. Universidad de la República; UruguayFil: Alvarez, Guzmán. Universidad de la República; UruguayFil: Benítez, Diego. Universidad de la República; UruguayFil: Boiani, Lucía. Universidad de la República; UruguayFil: Quiroga, Martín. No especifíca;Fil: Hernández, Paola. Universidad de la República; UruguayFil: Sortino, Maximiliano Andrés. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: González, Mercedes. Universidad de la República; UruguayFil: Cerecetto, Hugo. Universidad de la República; UruguayPergamon-Elsevier Science Ltd2009-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/130232Gerpe, Alejandra; Alvarez, Guzmán; Benítez, Diego; Boiani, Lucía; Quiroga, Martín; et al.; 5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene; Pergamon-Elsevier Science Ltd; Bioorganic & Medicinal Chemistry; 17; 21; 11-2009; 7500-75090968-0896CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0968089609008657info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bmc.2009.09.013info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:39Zoai:ri.conicet.gov.ar:11336/130232instacron: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:34982025-09-03 10:11:40.143CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene
title 5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene
spellingShingle 5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene
Gerpe, Alejandra
5-NITROTHIOPHENE
8-NITROFURAN
ANTI-TRYPANOSOMA CRUZI COMPOUNDS
SQUALENE EPOXIDASE
STEROL BIOSYNTHESIS INHIBITORS
title_short 5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene
title_full 5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene
title_fullStr 5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene
title_full_unstemmed 5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene
title_sort 5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene
dc.creator.none.fl_str_mv Gerpe, Alejandra
Alvarez, Guzmán
Benítez, Diego
Boiani, Lucía
Quiroga, Martín
Hernández, Paola
Sortino, Maximiliano Andrés
Zacchino, Susana Alicia Stella
González, Mercedes
Cerecetto, Hugo
author Gerpe, Alejandra
author_facet Gerpe, Alejandra
Alvarez, Guzmán
Benítez, Diego
Boiani, Lucía
Quiroga, Martín
Hernández, Paola
Sortino, Maximiliano Andrés
Zacchino, Susana Alicia Stella
González, Mercedes
Cerecetto, Hugo
author_role author
author2 Alvarez, Guzmán
Benítez, Diego
Boiani, Lucía
Quiroga, Martín
Hernández, Paola
Sortino, Maximiliano Andrés
Zacchino, Susana Alicia Stella
González, Mercedes
Cerecetto, Hugo
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv 5-NITROTHIOPHENE
8-NITROFURAN
ANTI-TRYPANOSOMA CRUZI COMPOUNDS
SQUALENE EPOXIDASE
STEROL BIOSYNTHESIS INHIBITORS
topic 5-NITROTHIOPHENE
8-NITROFURAN
ANTI-TRYPANOSOMA CRUZI COMPOUNDS
SQUALENE EPOXIDASE
STEROL BIOSYNTHESIS INHIBITORS
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 serious public health problem in South America. The first line of treatment is Nifurtimox and Benznidazole which generate toxic effects in treated patients. We have recently shown that a number of 5-nitrofuranes possess activity against Trypanosoma cruzi through oxidative stress and inhibition of parasite ergosterol biosynthesis, specifically at the level of squalene epoxidase. Here, we identify new 5-nitrofuranes and the thia-analogues with excellent effects on the viability of T. cruzi and adequate parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated, during 120 h, with the compounds showed that some of them accumulated squalene suggesting the squalene epoxidase activity inhibition of the parasite. Nifurtimox was able to accumulate squalene only at lower incubation times. Due to this fact some derivatives were also tested as antifungal agents. Quantitative structure-activity relationship studies were also performed showing relevant features for further new derivatives design. Taken together, the results obtained in the present work point to a more general effect of 5-nitrofuranes and 5-nitrothiophenes in trypanosomatids, opening potential therapeutic possibilities of them for these infectious diseases.
Fil: Gerpe, Alejandra. Universidad de la República; Uruguay
Fil: Alvarez, Guzmán. Universidad de la República; Uruguay
Fil: Benítez, Diego. Universidad de la República; Uruguay
Fil: Boiani, Lucía. Universidad de la República; Uruguay
Fil: Quiroga, Martín. No especifíca;
Fil: Hernández, Paola. Universidad de la República; Uruguay
Fil: Sortino, Maximiliano Andrés. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: González, Mercedes. Universidad de la República; Uruguay
Fil: Cerecetto, Hugo. Universidad de la República; Uruguay
description Chagas disease represents a serious public health problem in South America. The first line of treatment is Nifurtimox and Benznidazole which generate toxic effects in treated patients. We have recently shown that a number of 5-nitrofuranes possess activity against Trypanosoma cruzi through oxidative stress and inhibition of parasite ergosterol biosynthesis, specifically at the level of squalene epoxidase. Here, we identify new 5-nitrofuranes and the thia-analogues with excellent effects on the viability of T. cruzi and adequate parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated, during 120 h, with the compounds showed that some of them accumulated squalene suggesting the squalene epoxidase activity inhibition of the parasite. Nifurtimox was able to accumulate squalene only at lower incubation times. Due to this fact some derivatives were also tested as antifungal agents. Quantitative structure-activity relationship studies were also performed showing relevant features for further new derivatives design. Taken together, the results obtained in the present work point to a more general effect of 5-nitrofuranes and 5-nitrothiophenes in trypanosomatids, opening potential therapeutic possibilities of them for these infectious diseases.
publishDate 2009
dc.date.none.fl_str_mv 2009-11
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/11336/130232
Gerpe, Alejandra; Alvarez, Guzmán; Benítez, Diego; Boiani, Lucía; Quiroga, Martín; et al.; 5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene; Pergamon-Elsevier Science Ltd; Bioorganic & Medicinal Chemistry; 17; 21; 11-2009; 7500-7509
0968-0896
CONICET Digital
CONICET
url http://hdl.handle.net/11336/130232
identifier_str_mv Gerpe, Alejandra; Alvarez, Guzmán; Benítez, Diego; Boiani, Lucía; Quiroga, Martín; et al.; 5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene; Pergamon-Elsevier Science Ltd; Bioorganic & Medicinal Chemistry; 17; 21; 11-2009; 7500-7509
0968-0896
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://www.sciencedirect.com/science/article/abs/pii/S0968089609008657
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bmc.2009.09.013
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
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
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 13.13397

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