Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibition

Autores
Prieto, Julián José; Talevi, Alan; Bruno Blanch, Luis Enrique
Año de publicación
2006
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We have performed virtual screening to identify new lead trypanothione reductase inhibitor (TRI) compounds, enzyme present in Tripanozoma cruzi, the agent responsible of Chagas disease. From a training set of 58 compounds, linear discriminant analysis (LDA) was performed using 2D and 3D descriptors as discriminating variables in order to find out which function of descriptors characterizes the active TRI. The values of the statistical parameters F - Snedecor and Wilk's λ for the discriminant function (DF) showed good statistical significance, as long as the rate of success in the prediction for both the training and the test set: 91.38% and 88.63%, in that order. Internal validation through the Leave — Group — Out methodology was performed with good results, assuring the stability of the DF. Afterwards, the DF was applied in virtual screening of 422,367 compounds. The optimum range of values of octanol — water partition coefficient for a compound to develop trypanothione reductase inhibition was applied as a second filtering criteria. 739 structurally heterogeneous drugs of the virtual library were selected as promissory TRI.
Facultad de Ciencias Exactas
Materia
Ciencias Exactas
Medicina
Linear Discriminant Analysis
virtual screening
trypanothione reductase inhibitor
Trypanosoma cruzi
Chagas disease
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/131964

id SEDICI_06ad2e16c5a74614acd8656d79a82a5e
oai_identifier_str oai:sedici.unlp.edu.ar:10915/131964
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibitionPrieto, Julián JoséTalevi, AlanBruno Blanch, Luis EnriqueCiencias ExactasMedicinaLinear Discriminant Analysisvirtual screeningtrypanothione reductase inhibitorTrypanosoma cruziChagas diseaseWe have performed virtual screening to identify new lead trypanothione reductase inhibitor (TRI) compounds, enzyme present in <i>Tripanozoma cruzi</i>, the agent responsible of Chagas disease. From a training set of 58 compounds, linear discriminant analysis (LDA) was performed using 2D and 3D descriptors as discriminating variables in order to find out which function of descriptors characterizes the active TRI. The values of the statistical parameters F - Snedecor and Wilk's λ for the discriminant function (DF) showed good statistical significance, as long as the rate of success in the prediction for both the training and the test set: 91.38% and 88.63%, in that order. Internal validation through the Leave — Group — Out methodology was performed with good results, assuring the stability of the DF. Afterwards, the DF was applied in virtual screening of 422,367 compounds. The optimum range of values of octanol — water partition coefficient for a compound to develop trypanothione reductase inhibition was applied as a second filtering criteria. 739 structurally heterogeneous drugs of the virtual library were selected as promissory TRI.Facultad de Ciencias Exactas2006-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf361-375http://sedici.unlp.edu.ar/handle/10915/131964enginfo:eu-repo/semantics/altIdentifier/issn/1381-1991info:eu-repo/semantics/altIdentifier/issn/1573-501Xinfo:eu-repo/semantics/altIdentifier/doi/10.1007/s11030-006-9044-2info:eu-repo/semantics/altIdentifier/pmid/17031538info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:32:26Zoai:sedici.unlp.edu.ar:10915/131964Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:32:27.038SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibition
title Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibition
spellingShingle Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibition
Prieto, Julián José
Ciencias Exactas
Medicina
Linear Discriminant Analysis
virtual screening
trypanothione reductase inhibitor
Trypanosoma cruzi
Chagas disease
title_short Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibition
title_full Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibition
title_fullStr Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibition
title_full_unstemmed Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibition
title_sort Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibition
dc.creator.none.fl_str_mv Prieto, Julián José
Talevi, Alan
Bruno Blanch, Luis Enrique
author Prieto, Julián José
author_facet Prieto, Julián José
Talevi, Alan
Bruno Blanch, Luis Enrique
author_role author
author2 Talevi, Alan
Bruno Blanch, Luis Enrique
author2_role author
author
dc.subject.none.fl_str_mv Ciencias Exactas
Medicina
Linear Discriminant Analysis
virtual screening
trypanothione reductase inhibitor
Trypanosoma cruzi
Chagas disease
topic Ciencias Exactas
Medicina
Linear Discriminant Analysis
virtual screening
trypanothione reductase inhibitor
Trypanosoma cruzi
Chagas disease
dc.description.none.fl_txt_mv We have performed virtual screening to identify new lead trypanothione reductase inhibitor (TRI) compounds, enzyme present in <i>Tripanozoma cruzi</i>, the agent responsible of Chagas disease. From a training set of 58 compounds, linear discriminant analysis (LDA) was performed using 2D and 3D descriptors as discriminating variables in order to find out which function of descriptors characterizes the active TRI. The values of the statistical parameters F - Snedecor and Wilk's λ for the discriminant function (DF) showed good statistical significance, as long as the rate of success in the prediction for both the training and the test set: 91.38% and 88.63%, in that order. Internal validation through the Leave — Group — Out methodology was performed with good results, assuring the stability of the DF. Afterwards, the DF was applied in virtual screening of 422,367 compounds. The optimum range of values of octanol — water partition coefficient for a compound to develop trypanothione reductase inhibition was applied as a second filtering criteria. 739 structurally heterogeneous drugs of the virtual library were selected as promissory TRI.
Facultad de Ciencias Exactas
description We have performed virtual screening to identify new lead trypanothione reductase inhibitor (TRI) compounds, enzyme present in <i>Tripanozoma cruzi</i>, the agent responsible of Chagas disease. From a training set of 58 compounds, linear discriminant analysis (LDA) was performed using 2D and 3D descriptors as discriminating variables in order to find out which function of descriptors characterizes the active TRI. The values of the statistical parameters F - Snedecor and Wilk's λ for the discriminant function (DF) showed good statistical significance, as long as the rate of success in the prediction for both the training and the test set: 91.38% and 88.63%, in that order. Internal validation through the Leave — Group — Out methodology was performed with good results, assuring the stability of the DF. Afterwards, the DF was applied in virtual screening of 422,367 compounds. The optimum range of values of octanol — water partition coefficient for a compound to develop trypanothione reductase inhibition was applied as a second filtering criteria. 739 structurally heterogeneous drugs of the virtual library were selected as promissory TRI.
publishDate 2006
dc.date.none.fl_str_mv 2006-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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://sedici.unlp.edu.ar/handle/10915/131964
url http://sedici.unlp.edu.ar/handle/10915/131964
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1381-1991
info:eu-repo/semantics/altIdentifier/issn/1573-501X
info:eu-repo/semantics/altIdentifier/doi/10.1007/s11030-006-9044-2
info:eu-repo/semantics/altIdentifier/pmid/17031538
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
361-375
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
_version_ 1844616203590434816
score 13.070432