Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake

Autores
Alberca, Lucas Nicolás; Sbaraglini, Maria Laura; Morales, Juan Francisco; Dietrich, Roque Carlos; Ruiz, María Daniela; Pino Martínez, Agustina María; Miranda, Cristian Gabriel; Fraccaroli, Laura Virginia; Alba Soto, Catalina Dirney; Carrillo, Carolina; Palestro, Pablo Hernán; Talevi, Alan
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas disease is a neglected tropical disease endemic to Latin America, though migratory movements have recently spread it to other regions. Here, we have applied a cascade virtual screening campaign combining ligand- and structure-based methods. In order to find novel inhibitors of putrescine uptake in Trypanosoma cruzi, an ensemble of linear ligand-based classifiers obtained by has been applied as initial screening filter, followed by docking into a homology model of the putrescine permease TcPAT12. 1,000 individual linear classifiers were inferred from a balanced dataset. Subsequently, different schemes were tested to combine the individual classifiers: MIN operator, average ranking, average score, average voting, with MIN operator leading to the best performance. The homology model was based on the arginine/agmatine antiporter (AdiC) from Escherichia coli as template. It showed 64% coverage of the entire query sequence and it was selected based on the normalized Discrete Optimized Protein Energy parameter and the GA341 score. The modeled structure had 96% in the allowed area of Ramachandran's plot, and none of the residues located in non-allowed regions were involved in the active site of the transporter. Positivity Predictive Value surfaces were applied to optimize the score thresholds to be used in the ligand-based virtual screening step: for that purpose Positivity Predictive Value was charted as a function of putative yields of active in the range 0.001-0.010 and the Se/Sp ratio. With a focus on drug repositioning opportunities, DrugBank and Sweetlead databases were subjected to screening. Among 8 hits, cinnarizine, a drug frequently prescribed for motion sickness and balance disorder, was tested against T. cruzi epimastigotes and amastigotes, confirming its trypanocidal effects and its inhibitory effects on putrescine uptake. Furthermore, clofazimine, an antibiotic with already proven trypanocidal effects, also displayed inhibitory effects on putrescine uptake. Two other hits, meclizine and butoconazole, also displayed trypanocidal effects (in the case of meclizine, against both epimastigotes and amastigotes), without inhibiting putrescine uptake.
Fil: Alberca, Lucas Nicolás. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; Argentina
Fil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; Argentina
Fil: Morales, Juan Francisco. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; Argentina
Fil: Dietrich, Roque Carlos. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; Argentina
Fil: Ruiz, María Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; Argentina
Fil: Pino Martínez, Agustina María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Miranda, Cristian Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Fraccaroli, Laura Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; Argentina
Fil: Alba Soto, Catalina Dirney. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Carrillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; Argentina
Fil: Palestro, Pablo Hernán. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; Argentina
Fil: Talevi, Alan. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; Argentina
Materia
CHAGAS DISEASE
CINNARIZINE
DRUG REPOSITIONING
DRUG REPURPOSING
POSITIVE PREDICTIVE VALUE
PUTRESCINE UPTAKE
TRYPANOSOMA CRUZI
VIRTUAL SCREENING
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/94582
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptakeAlberca, Lucas NicolásSbaraglini, Maria LauraMorales, Juan FranciscoDietrich, Roque CarlosRuiz, María DanielaPino Martínez, Agustina MaríaMiranda, Cristian GabrielFraccaroli, Laura VirginiaAlba Soto, Catalina DirneyCarrillo, CarolinaPalestro, Pablo HernánTalevi, AlanCHAGAS DISEASECINNARIZINEDRUG REPOSITIONINGDRUG REPURPOSINGPOSITIVE PREDICTIVE VALUEPUTRESCINE UPTAKETRYPANOSOMA CRUZIVIRTUAL SCREENINGhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Chagas disease is a neglected tropical disease endemic to Latin America, though migratory movements have recently spread it to other regions. Here, we have applied a cascade virtual screening campaign combining ligand- and structure-based methods. In order to find novel inhibitors of putrescine uptake in Trypanosoma cruzi, an ensemble of linear ligand-based classifiers obtained by has been applied as initial screening filter, followed by docking into a homology model of the putrescine permease TcPAT12. 1,000 individual linear classifiers were inferred from a balanced dataset. Subsequently, different schemes were tested to combine the individual classifiers: MIN operator, average ranking, average score, average voting, with MIN operator leading to the best performance. The homology model was based on the arginine/agmatine antiporter (AdiC) from Escherichia coli as template. It showed 64% coverage of the entire query sequence and it was selected based on the normalized Discrete Optimized Protein Energy parameter and the GA341 score. The modeled structure had 96% in the allowed area of Ramachandran's plot, and none of the residues located in non-allowed regions were involved in the active site of the transporter. Positivity Predictive Value surfaces were applied to optimize the score thresholds to be used in the ligand-based virtual screening step: for that purpose Positivity Predictive Value was charted as a function of putative yields of active in the range 0.001-0.010 and the Se/Sp ratio. With a focus on drug repositioning opportunities, DrugBank and Sweetlead databases were subjected to screening. Among 8 hits, cinnarizine, a drug frequently prescribed for motion sickness and balance disorder, was tested against T. cruzi epimastigotes and amastigotes, confirming its trypanocidal effects and its inhibitory effects on putrescine uptake. Furthermore, clofazimine, an antibiotic with already proven trypanocidal effects, also displayed inhibitory effects on putrescine uptake. Two other hits, meclizine and butoconazole, also displayed trypanocidal effects (in the case of meclizine, against both epimastigotes and amastigotes), without inhibiting putrescine uptake.Fil: Alberca, Lucas Nicolás. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; ArgentinaFil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; ArgentinaFil: Morales, Juan Francisco. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; ArgentinaFil: Dietrich, Roque Carlos. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; ArgentinaFil: Ruiz, María Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Pino Martínez, Agustina María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Miranda, Cristian Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Fraccaroli, Laura Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Alba Soto, Catalina Dirney. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Carrillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Palestro, Pablo Hernán. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; ArgentinaFil: Talevi, Alan. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; ArgentinaFrontiers Media SA2018-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/94582Alberca, Lucas Nicolás; Sbaraglini, Maria Laura; Morales, Juan Francisco; Dietrich, Roque Carlos; Ruiz, María Daniela; et al.; Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake; Frontiers Media SA; Frontiers in Cellular and Infection Microbiology; 8; 173; 5-2018; 1-152235-2988CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fcimb.2018.00173/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fcimb.2018.00173info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981162/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:14:33Zoai:ri.conicet.gov.ar:11336/94582instacron: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:34982025-09-10 13:14:33.815CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake
title Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake
spellingShingle Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake
Alberca, Lucas Nicolás
CHAGAS DISEASE
CINNARIZINE
DRUG REPOSITIONING
DRUG REPURPOSING
POSITIVE PREDICTIVE VALUE
PUTRESCINE UPTAKE
TRYPANOSOMA CRUZI
VIRTUAL SCREENING
title_short Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake
title_full Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake
title_fullStr Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake
title_full_unstemmed Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake
title_sort Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake
dc.creator.none.fl_str_mv Alberca, Lucas Nicolás
Sbaraglini, Maria Laura
Morales, Juan Francisco
Dietrich, Roque Carlos
Ruiz, María Daniela
Pino Martínez, Agustina María
Miranda, Cristian Gabriel
Fraccaroli, Laura Virginia
Alba Soto, Catalina Dirney
Carrillo, Carolina
Palestro, Pablo Hernán
Talevi, Alan
author Alberca, Lucas Nicolás
author_facet Alberca, Lucas Nicolás
Sbaraglini, Maria Laura
Morales, Juan Francisco
Dietrich, Roque Carlos
Ruiz, María Daniela
Pino Martínez, Agustina María
Miranda, Cristian Gabriel
Fraccaroli, Laura Virginia
Alba Soto, Catalina Dirney
Carrillo, Carolina
Palestro, Pablo Hernán
Talevi, Alan
author_role author
author2 Sbaraglini, Maria Laura
Morales, Juan Francisco
Dietrich, Roque Carlos
Ruiz, María Daniela
Pino Martínez, Agustina María
Miranda, Cristian Gabriel
Fraccaroli, Laura Virginia
Alba Soto, Catalina Dirney
Carrillo, Carolina
Palestro, Pablo Hernán
Talevi, Alan
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CHAGAS DISEASE
CINNARIZINE
DRUG REPOSITIONING
DRUG REPURPOSING
POSITIVE PREDICTIVE VALUE
PUTRESCINE UPTAKE
TRYPANOSOMA CRUZI
VIRTUAL SCREENING
topic CHAGAS DISEASE
CINNARIZINE
DRUG REPOSITIONING
DRUG REPURPOSING
POSITIVE PREDICTIVE VALUE
PUTRESCINE UPTAKE
TRYPANOSOMA CRUZI
VIRTUAL SCREENING
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chagas disease is a neglected tropical disease endemic to Latin America, though migratory movements have recently spread it to other regions. Here, we have applied a cascade virtual screening campaign combining ligand- and structure-based methods. In order to find novel inhibitors of putrescine uptake in Trypanosoma cruzi, an ensemble of linear ligand-based classifiers obtained by has been applied as initial screening filter, followed by docking into a homology model of the putrescine permease TcPAT12. 1,000 individual linear classifiers were inferred from a balanced dataset. Subsequently, different schemes were tested to combine the individual classifiers: MIN operator, average ranking, average score, average voting, with MIN operator leading to the best performance. The homology model was based on the arginine/agmatine antiporter (AdiC) from Escherichia coli as template. It showed 64% coverage of the entire query sequence and it was selected based on the normalized Discrete Optimized Protein Energy parameter and the GA341 score. The modeled structure had 96% in the allowed area of Ramachandran's plot, and none of the residues located in non-allowed regions were involved in the active site of the transporter. Positivity Predictive Value surfaces were applied to optimize the score thresholds to be used in the ligand-based virtual screening step: for that purpose Positivity Predictive Value was charted as a function of putative yields of active in the range 0.001-0.010 and the Se/Sp ratio. With a focus on drug repositioning opportunities, DrugBank and Sweetlead databases were subjected to screening. Among 8 hits, cinnarizine, a drug frequently prescribed for motion sickness and balance disorder, was tested against T. cruzi epimastigotes and amastigotes, confirming its trypanocidal effects and its inhibitory effects on putrescine uptake. Furthermore, clofazimine, an antibiotic with already proven trypanocidal effects, also displayed inhibitory effects on putrescine uptake. Two other hits, meclizine and butoconazole, also displayed trypanocidal effects (in the case of meclizine, against both epimastigotes and amastigotes), without inhibiting putrescine uptake.
Fil: Alberca, Lucas Nicolás. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; Argentina
Fil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; Argentina
Fil: Morales, Juan Francisco. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; Argentina
Fil: Dietrich, Roque Carlos. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; Argentina
Fil: Ruiz, María Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; Argentina
Fil: Pino Martínez, Agustina María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Miranda, Cristian Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Fraccaroli, Laura Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; Argentina
Fil: Alba Soto, Catalina Dirney. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Carrillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; Argentina
Fil: Palestro, Pablo Hernán. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; Argentina
Fil: Talevi, Alan. Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Departamento de Ciencia Biológica, Laboratorio de Investigación y Desarrollo de Compuestos Bioactivos; Argentina
description Chagas disease is a neglected tropical disease endemic to Latin America, though migratory movements have recently spread it to other regions. Here, we have applied a cascade virtual screening campaign combining ligand- and structure-based methods. In order to find novel inhibitors of putrescine uptake in Trypanosoma cruzi, an ensemble of linear ligand-based classifiers obtained by has been applied as initial screening filter, followed by docking into a homology model of the putrescine permease TcPAT12. 1,000 individual linear classifiers were inferred from a balanced dataset. Subsequently, different schemes were tested to combine the individual classifiers: MIN operator, average ranking, average score, average voting, with MIN operator leading to the best performance. The homology model was based on the arginine/agmatine antiporter (AdiC) from Escherichia coli as template. It showed 64% coverage of the entire query sequence and it was selected based on the normalized Discrete Optimized Protein Energy parameter and the GA341 score. The modeled structure had 96% in the allowed area of Ramachandran's plot, and none of the residues located in non-allowed regions were involved in the active site of the transporter. Positivity Predictive Value surfaces were applied to optimize the score thresholds to be used in the ligand-based virtual screening step: for that purpose Positivity Predictive Value was charted as a function of putative yields of active in the range 0.001-0.010 and the Se/Sp ratio. With a focus on drug repositioning opportunities, DrugBank and Sweetlead databases were subjected to screening. Among 8 hits, cinnarizine, a drug frequently prescribed for motion sickness and balance disorder, was tested against T. cruzi epimastigotes and amastigotes, confirming its trypanocidal effects and its inhibitory effects on putrescine uptake. Furthermore, clofazimine, an antibiotic with already proven trypanocidal effects, also displayed inhibitory effects on putrescine uptake. Two other hits, meclizine and butoconazole, also displayed trypanocidal effects (in the case of meclizine, against both epimastigotes and amastigotes), without inhibiting putrescine uptake.
publishDate 2018
dc.date.none.fl_str_mv 2018-05
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/11336/94582
Alberca, Lucas Nicolás; Sbaraglini, Maria Laura; Morales, Juan Francisco; Dietrich, Roque Carlos; Ruiz, María Daniela; et al.; Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake; Frontiers Media SA; Frontiers in Cellular and Infection Microbiology; 8; 173; 5-2018; 1-15
2235-2988
CONICET Digital
CONICET
url http://hdl.handle.net/11336/94582
identifier_str_mv Alberca, Lucas Nicolás; Sbaraglini, Maria Laura; Morales, Juan Francisco; Dietrich, Roque Carlos; Ruiz, María Daniela; et al.; Cascade ligand- and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake; Frontiers Media SA; Frontiers in Cellular and Infection Microbiology; 8; 173; 5-2018; 1-15
2235-2988
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fcimb.2018.00173/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fcimb.2018.00173
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981162/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
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dc.publisher.none.fl_str_mv Frontiers Media SA
publisher.none.fl_str_mv Frontiers Media SA
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
repository.name.fl_str_mv 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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