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dc.contributor.author
Comelli, Nieves Carolina
dc.contributor.author
Duchowicz, Pablo Román
dc.contributor.author
Castro, Eduardo Alberto
dc.date.available
2016-04-18T20:54:53Z
dc.date.issued
2014-05
dc.identifier.citation
Comelli, Nieves Carolina; Duchowicz, Pablo Román; Castro, Eduardo Alberto; QSAR models for thiophene and imidazopyridine derivatives inhibitors of the Polo-Like Kinase 1; Elsevier Science; European Journal Of Pharmaceutical Sciences; 62; 5-2014; 171-179
dc.identifier.issn
0928-0987
dc.identifier.uri
http://hdl.handle.net/11336/5267
dc.description.abstract
The inhibitory activity of 103 thiophene and 33 imidazopyridine derivatives against Polo-Like Kinase 1 (PLK1) expressed as pIC50 (log IC50) was predicted by QSAR modeling. Multivariate linear regression (MLR) was employed to model the relationship between 0D and 3D molecular descriptors and biological activities of molecules using the replacement method (MR) as variable selection tool. The 136 compounds were separated into several training and test sets. Two splitting approaches, distribution of biological data and structural diversity, and the statistical experimental design procedure Doptimal distance were applied to the dataset. The significance of the training set models was confirmed by statistically higher values of the internal leave one out cross-validated coefficient of determination (Q2) and external predictive coefficient of determination for the test set (R2 test). The model developed from a training set, obtained with the D-optimal distance protocol and using 3D descriptor space along with activity values, separated chemical features that allowed to distinguish high and low pIC50 values reasonably well. Then, we verified that such model was sufficient to reliably and accurately predict the activity of external diverse structures. The model robustness was properly characterized by means of standard procedures and their applicability domain (AD) was analyzed by leverage method.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Chemoinformatics
dc.subject
Multivariate Linear Regression Analysis
dc.subject
Polo-Like Kinase 1 (Plk1) Inhibitors
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Thiophene And Imidazopyridines Derivatives
dc.subject.classification
Farmacología y Farmacia
dc.subject.classification
Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
QSAR models for thiophene and imidazopyridine derivatives inhibitors of the Polo-Like Kinase 1
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-05-06 15:52:43.262787-03
dc.journal.volume
62
dc.journal.pagination
171-179
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Comelli, Nieves Carolina. Universidad Nacional de Catamarca. Facultad de Ciencias Agrarias; Argentina
dc.description.fil
Fil: Duchowicz, Pablo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
dc.description.fil
Fil: Castro, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
dc.journal.title
European Journal Of Pharmaceutical Sciences
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0928098714002589
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.ejps.2014.05.029
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