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dc.contributor.author
Garcia Liñares, Guadalupe Eugenia
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Zígolo, M. Antonela
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Simonetti, Leandro
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Longhi, Silvia Andrea
dc.contributor.author
Baldessari, Alicia
dc.date.available
2016-02-01T20:31:34Z
dc.date.issued
2015-05-30
dc.identifier.citation
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
dc.identifier.issn
0968-0896
dc.identifier.uri
http://hdl.handle.net/11336/3947
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Bile Acids
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Lipase-Catalyzed
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Molecular Modeling
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Chagas Disease
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Química Orgánica
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Ciencias Químicas
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CIENCIAS NATURALES Y EXACTAS
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Enfermedades Infecciosas
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
23
dc.journal.number
15
dc.journal.pagination
4804–4814
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
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
dc.description.fil
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
dc.description.fil
Fil: Simonetti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
dc.description.fil
Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
dc.description.fil
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
dc.journal.title
Bioorganic & Medicinal Chemistry
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0968089615004459
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bmc.2015.05.035
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/issn/0968-0896
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