Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi
- Autores
- Garcia Liñares, Guadalupe Eugenia; Zígolo, M. Antonela; Simonetti, Leandro; Longhi, Silvia Andrea; Baldessari, Alicia
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Enzyme catalysis was applied to synthesize derivatives of three bile acids and their biological activity was evaluated as growth inhibitors of the protozoan Trypanosoma cruzi. Twelve mono-, diacetyl and ester derivatives of deoxycholic, chenodeoxycholic and lithocholic acid, seven of them new compounds, were obtained through lipase-catalyzed acetylation, esterification and alcoholysis reactions in very good to excellent yield and a highly regioselective way. Among them, acetylated ester products, in which the lipase catalyzed both reactions in one-pot, were obtained. The influence of various reaction parameters in the enzymatic reactions, such as enzyme source, acylating agent/substrate ratio, enzyme/substrate ratio, solvent and temperature, was studied. Some of the evaluated compounds showed a remarkable activity as Trypanosoma cruzi growth inhibitors, obtaining the best results with ethyl chenodeoxycholate 3-acetate and chenodeoxycholic acid 3,7-diacetate, which showed IC50: 8.6 and 22.8μM, respectively. In addition, in order to shed light to bile acids behavior in enzymatic reactions, molecular modeling was applied to some derivatives. The advantages showed by the enzymatic methodology, such as mild reaction conditions and low environmental impact, make the biocatalysis a convenient way to synthesize these bile acid derivatives with application as potential antiparasitic agents.
Fil: Garcia Liñares, Guadalupe Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); Argentina
Fil: Zígolo, M. Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); Argentina
Fil: Simonetti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
Fil: Baldessari, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); Argentina - Materia
-
Bile Acids
Lipase-Catalyzed
Molecular Modeling
Chagas Disease - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/3947
Ver los metadatos del registro completo
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Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruziGarcia Liñares, Guadalupe EugeniaZígolo, M. AntonelaSimonetti, LeandroLonghi, Silvia AndreaBaldessari, AliciaBile AcidsLipase-CatalyzedMolecular ModelingChagas Diseasehttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Enzyme catalysis was applied to synthesize derivatives of three bile acids and their biological activity was evaluated as growth inhibitors of the protozoan Trypanosoma cruzi. Twelve mono-, diacetyl and ester derivatives of deoxycholic, chenodeoxycholic and lithocholic acid, seven of them new compounds, were obtained through lipase-catalyzed acetylation, esterification and alcoholysis reactions in very good to excellent yield and a highly regioselective way. Among them, acetylated ester products, in which the lipase catalyzed both reactions in one-pot, were obtained. The influence of various reaction parameters in the enzymatic reactions, such as enzyme source, acylating agent/substrate ratio, enzyme/substrate ratio, solvent and temperature, was studied. Some of the evaluated compounds showed a remarkable activity as Trypanosoma cruzi growth inhibitors, obtaining the best results with ethyl chenodeoxycholate 3-acetate and chenodeoxycholic acid 3,7-diacetate, which showed IC50: 8.6 and 22.8μM, respectively. In addition, in order to shed light to bile acids behavior in enzymatic reactions, molecular modeling was applied to some derivatives. The advantages showed by the enzymatic methodology, such as mild reaction conditions and low environmental impact, make the biocatalysis a convenient way to synthesize these bile acid derivatives with application as potential antiparasitic agents.Fil: Garcia Liñares, Guadalupe Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); ArgentinaFil: Zígolo, M. Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); ArgentinaFil: Simonetti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Baldessari, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); ArgentinaElsevier2015-05-30info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/3947Garcia Liñares, Guadalupe Eugenia; Zígolo, M. Antonela; Simonetti, Leandro; Longhi, Silvia Andrea; Baldessari, Alicia; Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi; Elsevier; Bioorganic & Medicinal Chemistry; 23; 15; 30-5-2015; 4804–48140968-0896enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0968089615004459info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bmc.2015.05.035info:eu-repo/semantics/altIdentifier/issn/0968-0896info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:56:59Zoai:ri.conicet.gov.ar:11336/3947instacron: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 09:57:00.227CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi |
title |
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi |
spellingShingle |
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi Garcia Liñares, Guadalupe Eugenia Bile Acids Lipase-Catalyzed Molecular Modeling Chagas Disease |
title_short |
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi |
title_full |
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi |
title_fullStr |
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi |
title_full_unstemmed |
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi |
title_sort |
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi |
dc.creator.none.fl_str_mv |
Garcia Liñares, Guadalupe Eugenia Zígolo, M. Antonela Simonetti, Leandro Longhi, Silvia Andrea Baldessari, Alicia |
author |
Garcia Liñares, Guadalupe Eugenia |
author_facet |
Garcia Liñares, Guadalupe Eugenia Zígolo, M. Antonela Simonetti, Leandro Longhi, Silvia Andrea Baldessari, Alicia |
author_role |
author |
author2 |
Zígolo, M. Antonela Simonetti, Leandro Longhi, Silvia Andrea Baldessari, Alicia |
author2_role |
author author author author |
dc.subject.none.fl_str_mv |
Bile Acids Lipase-Catalyzed Molecular Modeling Chagas Disease |
topic |
Bile Acids Lipase-Catalyzed Molecular Modeling Chagas Disease |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Enzyme catalysis was applied to synthesize derivatives of three bile acids and their biological activity was evaluated as growth inhibitors of the protozoan Trypanosoma cruzi. Twelve mono-, diacetyl and ester derivatives of deoxycholic, chenodeoxycholic and lithocholic acid, seven of them new compounds, were obtained through lipase-catalyzed acetylation, esterification and alcoholysis reactions in very good to excellent yield and a highly regioselective way. Among them, acetylated ester products, in which the lipase catalyzed both reactions in one-pot, were obtained. The influence of various reaction parameters in the enzymatic reactions, such as enzyme source, acylating agent/substrate ratio, enzyme/substrate ratio, solvent and temperature, was studied. Some of the evaluated compounds showed a remarkable activity as Trypanosoma cruzi growth inhibitors, obtaining the best results with ethyl chenodeoxycholate 3-acetate and chenodeoxycholic acid 3,7-diacetate, which showed IC50: 8.6 and 22.8μM, respectively. In addition, in order to shed light to bile acids behavior in enzymatic reactions, molecular modeling was applied to some derivatives. The advantages showed by the enzymatic methodology, such as mild reaction conditions and low environmental impact, make the biocatalysis a convenient way to synthesize these bile acid derivatives with application as potential antiparasitic agents. Fil: Garcia Liñares, Guadalupe Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); Argentina Fil: Zígolo, M. Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); Argentina Fil: Simonetti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina Fil: Baldessari, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); Argentina |
description |
Enzyme catalysis was applied to synthesize derivatives of three bile acids and their biological activity was evaluated as growth inhibitors of the protozoan Trypanosoma cruzi. Twelve mono-, diacetyl and ester derivatives of deoxycholic, chenodeoxycholic and lithocholic acid, seven of them new compounds, were obtained through lipase-catalyzed acetylation, esterification and alcoholysis reactions in very good to excellent yield and a highly regioselective way. Among them, acetylated ester products, in which the lipase catalyzed both reactions in one-pot, were obtained. The influence of various reaction parameters in the enzymatic reactions, such as enzyme source, acylating agent/substrate ratio, enzyme/substrate ratio, solvent and temperature, was studied. Some of the evaluated compounds showed a remarkable activity as Trypanosoma cruzi growth inhibitors, obtaining the best results with ethyl chenodeoxycholate 3-acetate and chenodeoxycholic acid 3,7-diacetate, which showed IC50: 8.6 and 22.8μM, respectively. In addition, in order to shed light to bile acids behavior in enzymatic reactions, molecular modeling was applied to some derivatives. The advantages showed by the enzymatic methodology, such as mild reaction conditions and low environmental impact, make the biocatalysis a convenient way to synthesize these bile acid derivatives with application as potential antiparasitic agents. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-05-30 |
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/11336/3947 Garcia Liñares, Guadalupe Eugenia; Zígolo, M. Antonela; Simonetti, Leandro; Longhi, Silvia Andrea; Baldessari, Alicia; Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi; Elsevier; Bioorganic & Medicinal Chemistry; 23; 15; 30-5-2015; 4804–4814 0968-0896 |
url |
http://hdl.handle.net/11336/3947 |
identifier_str_mv |
Garcia Liñares, Guadalupe Eugenia; Zígolo, M. Antonela; Simonetti, Leandro; Longhi, Silvia Andrea; Baldessari, Alicia; Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi; Elsevier; Bioorganic & Medicinal Chemistry; 23; 15; 30-5-2015; 4804–4814 0968-0896 |
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/S0968089615004459 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bmc.2015.05.035 info:eu-repo/semantics/altIdentifier/issn/0968-0896 |
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 |
publisher.none.fl_str_mv |
Elsevier |
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 |
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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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13.070432 |