Diisopropylphenyl-imidazole (DII): a new compound that exerts anthelmintic activity through novel molecular mechanisms

Autores
Blanco, Maria Gabriela; Vela Gurovic, Maria Soledad; Silbestri, Gustavo Fabián; Garelli, Andres; Giunti, Sebastián; Rayes, Diego Hernán; de Rosa, Maria Jose
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Nematode parasites cause infections that affect approximately one-third of the world ́s population and considerable losses in livestock and food crops. Paradoxically, the repertoire of effective anthelmintics for treating these parasitoses is very limited, as drug development has been delayed for decades. Moreover, resistance to currently available drugs is a global concern in livestock parasites and is an emerging issue for human helminthiasis. Therefore, anthelmintics with novel mechanisms of action are urgently needed. Taking advantage of Caenorhabditis elegans as an established model system for developing agents, in this project we synthesized and screened the anthelmintic potential of novel imidazolium and imidazole derivatives. We found that one of these derivatives, diisopropylphenyl-imidazole (DII), is lethal to C. elegans at both mature and immature stages. Toxicity appears to be specific because DII concentrations which are lethal to C. elegans do not induce significant lethality on bacteria, Drosophila melanogaster,and HEK-293 cells. Our analysis of DII action on C. elegans mutant strains determined that, in the adult stage, null mutants of unc-29 are resistant to the drug. Muscle expression of this gene completely restores DII sensitivity. UNC-29 was reported as an essential constituent of the levamisole-sensitive muscle nicotinic receptor (L-AChR). Nevertheless, null mutants in unc-63 and lev-8 (essential and non-essential subunits of L-AChRs, respectively) are as sensitive to DII as the wild-type strain. Therefore, our results suggest that DII effects on adult nematodes rely on a previously undescribed AChR. This novel AChR is composed by UNC-29 (a non-alfa subunit incapable of forming homomeric receptors) and other unidentified subunits. To completely elucidate its stoichiometry, we are analyzing DII resistance in different strains containing null mutations in AChR subunits. Since DII mechanism is different from those of currently used anthelmintics, it could constitute a therapeutic option when traditional anthelmintic agents fail. Interestingly, DII targets appear to be different between larvae and adults, as unc-29 null mutant larvae are sensitive to the drug. The existence of more than one target could delay resistance development. The specificity and novel mode of action of DII, which includes differential targeting in larvae and adult nematodes, support its potential as a promising drug candidate to treat helminthiasis.
Fil: Blanco, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Vela Gurovic, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina
Fil: Silbestri, Gustavo Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
Fil: Garelli, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Giunti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Rayes, Diego Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: de Rosa, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Reunión Anual de Sociedades de Biociencia: LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB;) XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP) y IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar)
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Materia
C ELEGANS
ANTHELMINTIC
NICOTINIC RECEPTOR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/160345
Acceder
id CONICETDig_bb437d87f9f0afa2ebfbf3215211d44d
oai_identifier_str oai:ri.conicet.gov.ar:11336/160345
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Diisopropylphenyl-imidazole (DII): a new compound that exerts anthelmintic activity through novel molecular mechanismsBlanco, Maria GabrielaVela Gurovic, Maria SoledadSilbestri, Gustavo FabiánGarelli, AndresGiunti, SebastiánRayes, Diego Hernánde Rosa, Maria JoseC ELEGANSANTHELMINTICNICOTINIC RECEPTORhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Nematode parasites cause infections that affect approximately one-third of the world ́s population and considerable losses in livestock and food crops. Paradoxically, the repertoire of effective anthelmintics for treating these parasitoses is very limited, as drug development has been delayed for decades. Moreover, resistance to currently available drugs is a global concern in livestock parasites and is an emerging issue for human helminthiasis. Therefore, anthelmintics with novel mechanisms of action are urgently needed. Taking advantage of Caenorhabditis elegans as an established model system for developing agents, in this project we synthesized and screened the anthelmintic potential of novel imidazolium and imidazole derivatives. We found that one of these derivatives, diisopropylphenyl-imidazole (DII), is lethal to C. elegans at both mature and immature stages. Toxicity appears to be specific because DII concentrations which are lethal to C. elegans do not induce significant lethality on bacteria, Drosophila melanogaster,and HEK-293 cells. Our analysis of DII action on C. elegans mutant strains determined that, in the adult stage, null mutants of unc-29 are resistant to the drug. Muscle expression of this gene completely restores DII sensitivity. UNC-29 was reported as an essential constituent of the levamisole-sensitive muscle nicotinic receptor (L-AChR). Nevertheless, null mutants in unc-63 and lev-8 (essential and non-essential subunits of L-AChRs, respectively) are as sensitive to DII as the wild-type strain. Therefore, our results suggest that DII effects on adult nematodes rely on a previously undescribed AChR. This novel AChR is composed by UNC-29 (a non-alfa subunit incapable of forming homomeric receptors) and other unidentified subunits. To completely elucidate its stoichiometry, we are analyzing DII resistance in different strains containing null mutations in AChR subunits. Since DII mechanism is different from those of currently used anthelmintics, it could constitute a therapeutic option when traditional anthelmintic agents fail. Interestingly, DII targets appear to be different between larvae and adults, as unc-29 null mutant larvae are sensitive to the drug. The existence of more than one target could delay resistance development. The specificity and novel mode of action of DII, which includes differential targeting in larvae and adult nematodes, support its potential as a promising drug candidate to treat helminthiasis.Fil: Blanco, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Vela Gurovic, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Silbestri, Gustavo Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Garelli, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Giunti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Rayes, Diego Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: de Rosa, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaReunión Anual de Sociedades de Biociencia: LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB;) XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP) y IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar)Mar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasFundación Revista Medicina2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/160345Diisopropylphenyl-imidazole (DII): a new compound that exerts anthelmintic activity through novel molecular mechanisms; Reunión Anual de Sociedades de Biociencia: LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB;) XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP) y IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); Mar del Plata; Argentina; 2019; 65-650025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:33:47Zoai:ri.conicet.gov.ar:11336/160345instacron: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:34982025-09-29 10:33:47.329CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Diisopropylphenyl-imidazole (DII): a new compound that exerts anthelmintic activity through novel molecular mechanisms
title Diisopropylphenyl-imidazole (DII): a new compound that exerts anthelmintic activity through novel molecular mechanisms
spellingShingle Diisopropylphenyl-imidazole (DII): a new compound that exerts anthelmintic activity through novel molecular mechanisms
Blanco, Maria Gabriela
C ELEGANS
ANTHELMINTIC
NICOTINIC RECEPTOR
title_short Diisopropylphenyl-imidazole (DII): a new compound that exerts anthelmintic activity through novel molecular mechanisms
title_full Diisopropylphenyl-imidazole (DII): a new compound that exerts anthelmintic activity through novel molecular mechanisms
title_fullStr Diisopropylphenyl-imidazole (DII): a new compound that exerts anthelmintic activity through novel molecular mechanisms
title_full_unstemmed Diisopropylphenyl-imidazole (DII): a new compound that exerts anthelmintic activity through novel molecular mechanisms
title_sort Diisopropylphenyl-imidazole (DII): a new compound that exerts anthelmintic activity through novel molecular mechanisms
dc.creator.none.fl_str_mv Blanco, Maria Gabriela
Vela Gurovic, Maria Soledad
Silbestri, Gustavo Fabián
Garelli, Andres
Giunti, Sebastián
Rayes, Diego Hernán
de Rosa, Maria Jose
author Blanco, Maria Gabriela
author_facet Blanco, Maria Gabriela
Vela Gurovic, Maria Soledad
Silbestri, Gustavo Fabián
Garelli, Andres
Giunti, Sebastián
Rayes, Diego Hernán
de Rosa, Maria Jose
author_role author
author2 Vela Gurovic, Maria Soledad
Silbestri, Gustavo Fabián
Garelli, Andres
Giunti, Sebastián
Rayes, Diego Hernán
de Rosa, Maria Jose
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv C ELEGANS
ANTHELMINTIC
NICOTINIC RECEPTOR
topic C ELEGANS
ANTHELMINTIC
NICOTINIC RECEPTOR
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Nematode parasites cause infections that affect approximately one-third of the world ́s population and considerable losses in livestock and food crops. Paradoxically, the repertoire of effective anthelmintics for treating these parasitoses is very limited, as drug development has been delayed for decades. Moreover, resistance to currently available drugs is a global concern in livestock parasites and is an emerging issue for human helminthiasis. Therefore, anthelmintics with novel mechanisms of action are urgently needed. Taking advantage of Caenorhabditis elegans as an established model system for developing agents, in this project we synthesized and screened the anthelmintic potential of novel imidazolium and imidazole derivatives. We found that one of these derivatives, diisopropylphenyl-imidazole (DII), is lethal to C. elegans at both mature and immature stages. Toxicity appears to be specific because DII concentrations which are lethal to C. elegans do not induce significant lethality on bacteria, Drosophila melanogaster,and HEK-293 cells. Our analysis of DII action on C. elegans mutant strains determined that, in the adult stage, null mutants of unc-29 are resistant to the drug. Muscle expression of this gene completely restores DII sensitivity. UNC-29 was reported as an essential constituent of the levamisole-sensitive muscle nicotinic receptor (L-AChR). Nevertheless, null mutants in unc-63 and lev-8 (essential and non-essential subunits of L-AChRs, respectively) are as sensitive to DII as the wild-type strain. Therefore, our results suggest that DII effects on adult nematodes rely on a previously undescribed AChR. This novel AChR is composed by UNC-29 (a non-alfa subunit incapable of forming homomeric receptors) and other unidentified subunits. To completely elucidate its stoichiometry, we are analyzing DII resistance in different strains containing null mutations in AChR subunits. Since DII mechanism is different from those of currently used anthelmintics, it could constitute a therapeutic option when traditional anthelmintic agents fail. Interestingly, DII targets appear to be different between larvae and adults, as unc-29 null mutant larvae are sensitive to the drug. The existence of more than one target could delay resistance development. The specificity and novel mode of action of DII, which includes differential targeting in larvae and adult nematodes, support its potential as a promising drug candidate to treat helminthiasis.
Fil: Blanco, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Vela Gurovic, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina
Fil: Silbestri, Gustavo Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
Fil: Garelli, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Giunti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Rayes, Diego Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: de Rosa, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Reunión Anual de Sociedades de Biociencia: LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB;) XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP) y IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar)
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
description Nematode parasites cause infections that affect approximately one-third of the world ́s population and considerable losses in livestock and food crops. Paradoxically, the repertoire of effective anthelmintics for treating these parasitoses is very limited, as drug development has been delayed for decades. Moreover, resistance to currently available drugs is a global concern in livestock parasites and is an emerging issue for human helminthiasis. Therefore, anthelmintics with novel mechanisms of action are urgently needed. Taking advantage of Caenorhabditis elegans as an established model system for developing agents, in this project we synthesized and screened the anthelmintic potential of novel imidazolium and imidazole derivatives. We found that one of these derivatives, diisopropylphenyl-imidazole (DII), is lethal to C. elegans at both mature and immature stages. Toxicity appears to be specific because DII concentrations which are lethal to C. elegans do not induce significant lethality on bacteria, Drosophila melanogaster,and HEK-293 cells. Our analysis of DII action on C. elegans mutant strains determined that, in the adult stage, null mutants of unc-29 are resistant to the drug. Muscle expression of this gene completely restores DII sensitivity. UNC-29 was reported as an essential constituent of the levamisole-sensitive muscle nicotinic receptor (L-AChR). Nevertheless, null mutants in unc-63 and lev-8 (essential and non-essential subunits of L-AChRs, respectively) are as sensitive to DII as the wild-type strain. Therefore, our results suggest that DII effects on adult nematodes rely on a previously undescribed AChR. This novel AChR is composed by UNC-29 (a non-alfa subunit incapable of forming homomeric receptors) and other unidentified subunits. To completely elucidate its stoichiometry, we are analyzing DII resistance in different strains containing null mutations in AChR subunits. Since DII mechanism is different from those of currently used anthelmintics, it could constitute a therapeutic option when traditional anthelmintic agents fail. Interestingly, DII targets appear to be different between larvae and adults, as unc-29 null mutant larvae are sensitive to the drug. The existence of more than one target could delay resistance development. The specificity and novel mode of action of DII, which includes differential targeting in larvae and adult nematodes, support its potential as a promising drug candidate to treat helminthiasis.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/160345
Diisopropylphenyl-imidazole (DII): a new compound that exerts anthelmintic activity through novel molecular mechanisms; Reunión Anual de Sociedades de Biociencia: LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB;) XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP) y IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); Mar del Plata; Argentina; 2019; 65-65
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/160345
identifier_str_mv Diisopropylphenyl-imidazole (DII): a new compound that exerts anthelmintic activity through novel molecular mechanisms; Reunión Anual de Sociedades de Biociencia: LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB;) XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP) y IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); Mar del Plata; Argentina; 2019; 65-65
0025-7680
1669-9106
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.saic.org.ar/revista-medicina
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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
_version_ 1844614353340334080
score 13.070432

Publicaciones similares