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dc.contributor.author
Chiari, Maria Eugenia
dc.contributor.author
Tosoni, Leonardo Daniel
dc.contributor.author
Joray, Mariana Belén
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Diaz Napal, Georgina Natalia
dc.contributor.author
Palacios, Sara Maria
dc.contributor.author
Ruiz, Gustavo Miguel
dc.contributor.author
Vera, Domingo Mariano Adolfo
dc.contributor.author
Carpinella, Maria Cecilia
dc.date.available
2018-07-04T15:05:50Z
dc.date.issued
2015-10
dc.identifier.citation
Chiari, Maria Eugenia; Tosoni, Leonardo Daniel; Joray, Mariana Belén; Diaz Napal, Georgina Natalia; Palacios, Sara Maria; et al.; The Inhibitory Activity of Plants from Central Argentina on p-Hydroxyphenylpyruvate Dioxygenase: Isolation and Mechanism of Inhibition of a Flavanone from Flourensia oolepis; Georg Thieme Verlag Kg; Planta Medica; 81; 15; 10-2015; 1382-1391
dc.identifier.issn
0032-0943
dc.identifier.uri
http://hdl.handle.net/11336/51165
dc.description.abstract
The enzyme 4-hydroxyphenylpyruvate dioxygenase catalyzes the second step in the tyrosine degradation pathway. In mammals, this enzyme is the molecular target of drugs used for the treatment of metabolic disorders associated with defects in the tyrosine catabolism, mainly the fatal hereditary disease tyrosinemia type 1. This study evaluated the inhibitory effect of 91 extracts on 4-hydroxyphenylpyruvate dioxygenase from mostly native plants from central Argentina. Flourensia oolepis ethanol extract showed itself to be the most effective, and bioguided fractionation yielded pinocembrin (1) as its active principle. This flavanone, with an IC50 value of 73.1 µM and a KI of 13.7 µM, behaved as a reversible inhibitor of the enzyme and as a noncompetitive inhibitor. Molecular modeling studies confirmed the inhibitory potency of 1 and explained its activity by means of in silico determination of its binding mode in comparison to inhibitors of known activity, cocrystallized with 4-hydroxyphenylpyruvate dioxygenase. The main structural determinants that confer its potency are discussed. Analysis of the binding mode of the flavanone 1 with 4-hydroxyphenylpyruvate dioxygenase revealed the basis of the noncompetitive reversible mechanism of inhibition at the molecular level, which seems to be a common feature in this ubiquitous family of natural compounds. The resulting information may establish the basis for obtaining novel 4-hydroxyphenylpyruvate dioxygenase inhibitors for the treatment of tyrosinemia type 1 and other disorders associated with tyrosinase catabolism.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Georg Thieme Verlag Kg
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Flourensia Oolepis
dc.subject
Hppd Inhibitors
dc.subject
Molecular Docking
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Pinocembrin
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Otras Ciencias Químicas
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Ciencias Químicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
The Inhibitory Activity of Plants from Central Argentina on p-Hydroxyphenylpyruvate Dioxygenase: Isolation and Mechanism of Inhibition of a Flavanone from Flourensia oolepis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-29T13:08:49Z
dc.identifier.eissn
1439-0221
dc.journal.volume
81
dc.journal.number
15
dc.journal.pagination
1382-1391
dc.journal.pais
Alemania
dc.journal.ciudad
Berlín
dc.description.fil
Fil: Chiari, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; Argentina
dc.description.fil
Fil: Tosoni, Leonardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina
dc.description.fil
Fil: Joray, Mariana Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; Argentina
dc.description.fil
Fil: Diaz Napal, Georgina Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; Argentina
dc.description.fil
Fil: Palacios, Sara Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; Argentina
dc.description.fil
Fil: Ruiz, Gustavo Miguel. Universidad Católica de Córdoba. Facultad de Ciencias Agropecuarias; Argentina
dc.description.fil
Fil: Vera, Domingo Mariano Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina
dc.description.fil
Fil: Carpinella, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; Argentina
dc.journal.title
Planta Medica
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1055/s-0035-1557864
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.thieme-connect.de/DOI/DOI?10.1055/s-0035-1557864
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