In vitro and ex vivo synergistic effect of pyrvinium pamoate combined with miltefosine and paromomycin against Leishmania

17 páginas, 11 figuras, 6 tablas.

Detalles Bibliográficos
Autores: Melcón-Fernández, Estela, Galli, Giulio, Balaña-Fouce, Rafael, García-Fernández, Nerea, Martínez Valladares, María, Reguera, Rosa M, García-Estrada, Carlos, Pérez-Pertejo, Yolanda
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/365886
Acceso en línea:http://hdl.handle.net/10261/365886
https://api.elsevier.com/content/abstract/scopus_id/85187255253
Access Level:acceso abierto
Palabra clave:Leishmania
Drug combinations
Drug repurposing
Intestinal organoids
Pyrvinium pamoate plus miltefosine
Pyrvinium pamoate plus paromomycin
http://metadata.un.org/sdg/12
Ensure sustainable consumption and production patterns
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spelling In vitro and ex vivo synergistic effect of pyrvinium pamoate combined with miltefosine and paromomycin against LeishmaniaMelcón-Fernández, EstelaGalli, GiulioBalaña-Fouce, RafaelGarcía-Fernández, NereaMartínez Valladares, MaríaReguera, Rosa MGarcía-Estrada, CarlosPérez-Pertejo, YolandaLeishmaniaDrug combinationsDrug repurposingIntestinal organoidsPyrvinium pamoate plus miltefosinePyrvinium pamoate plus paromomycinhttp://metadata.un.org/sdg/12Ensure sustainable consumption and production patternsLeishmaniaDrug combinations17 páginas, 11 figuras, 6 tablas.One of the major drawbacks of current treatments for neglected tropical diseases is the low safety of the drugs used and the emergence of resistance. Leishmaniasis is a group of neglected diseases caused by protozoa of the trypanosomatidae family that lacks preventive vaccines and whose pharmacological treatments are scarce and unsafe. Combination therapy is a strategy that could solve the above-mentioned problems, due to the participation of several mechanisms of action and the reduction in the amount of drug necessary to obtain the therapeutic effect. In addition, this approach also increases the odds of finding an effective drug following the repurposing strategy. From the previous screening of two collections of repositioning drugs, we found that pyrvinium pamoate had a potent leishmanicidal effect. For this reason, we decided to combine it separately with two clinically used leishmanicidal drugs, miltefosine and paromomycin. These combinations were tested in axenic amastigotes of Leishmania infantum obtained from bone marrow cells and in intramacrophagic amastigotes obtained from primary cultures of splenic cells, both cell types coming from experimentally infected mice. Some of the combinations showed synergistic behavior, especially in the case of the combination of pyrvinium pamoate with paromomycin, and exhibited low cytotoxicity and good tolerability on intestinal murine organoids, which reveal the potential of these combinations for the treatment of leishmaniasis.G.G. is supported by Grant PRE2021–096909 funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future”. N.G.-F. is supported by University of León.Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)European CommissionUniversidad de LeónMartínez Valladares, María [0000-0002-3723-1895]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/365886https://api.elsevier.com/content/abstract/scopus_id/85187255253reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI//PRE2021–096909Tropical medicine and infectious diseasehttp://dx.doi.org/doi.org/10.3390/tropicalmed9020030Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3658862026-05-22T06:33:51Z
dc.title.none.fl_str_mv In vitro and ex vivo synergistic effect of pyrvinium pamoate combined with miltefosine and paromomycin against Leishmania
title In vitro and ex vivo synergistic effect of pyrvinium pamoate combined with miltefosine and paromomycin against Leishmania
spellingShingle In vitro and ex vivo synergistic effect of pyrvinium pamoate combined with miltefosine and paromomycin against Leishmania
Melcón-Fernández, Estela
Leishmania
Drug combinations
Drug repurposing
Intestinal organoids
Pyrvinium pamoate plus miltefosine
Pyrvinium pamoate plus paromomycin
http://metadata.un.org/sdg/12
Ensure sustainable consumption and production patterns
Leishmania
Drug combinations
title_short In vitro and ex vivo synergistic effect of pyrvinium pamoate combined with miltefosine and paromomycin against Leishmania
title_full In vitro and ex vivo synergistic effect of pyrvinium pamoate combined with miltefosine and paromomycin against Leishmania
title_fullStr In vitro and ex vivo synergistic effect of pyrvinium pamoate combined with miltefosine and paromomycin against Leishmania
title_full_unstemmed In vitro and ex vivo synergistic effect of pyrvinium pamoate combined with miltefosine and paromomycin against Leishmania
title_sort In vitro and ex vivo synergistic effect of pyrvinium pamoate combined with miltefosine and paromomycin against Leishmania
dc.creator.none.fl_str_mv Melcón-Fernández, Estela
Galli, Giulio
Balaña-Fouce, Rafael
García-Fernández, Nerea
Martínez Valladares, María
Reguera, Rosa M
García-Estrada, Carlos
Pérez-Pertejo, Yolanda
author Melcón-Fernández, Estela
author_facet Melcón-Fernández, Estela
Galli, Giulio
Balaña-Fouce, Rafael
García-Fernández, Nerea
Martínez Valladares, María
Reguera, Rosa M
García-Estrada, Carlos
Pérez-Pertejo, Yolanda
author_role author
author2 Galli, Giulio
Balaña-Fouce, Rafael
García-Fernández, Nerea
Martínez Valladares, María
Reguera, Rosa M
García-Estrada, Carlos
Pérez-Pertejo, Yolanda
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
European Commission
Universidad de León
Martínez Valladares, María [0000-0002-3723-1895]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Leishmania
Drug combinations
Drug repurposing
Intestinal organoids
Pyrvinium pamoate plus miltefosine
Pyrvinium pamoate plus paromomycin
http://metadata.un.org/sdg/12
Ensure sustainable consumption and production patterns
Leishmania
Drug combinations
topic Leishmania
Drug combinations
Drug repurposing
Intestinal organoids
Pyrvinium pamoate plus miltefosine
Pyrvinium pamoate plus paromomycin
http://metadata.un.org/sdg/12
Ensure sustainable consumption and production patterns
Leishmania
Drug combinations
description 17 páginas, 11 figuras, 6 tablas.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/365886
https://api.elsevier.com/content/abstract/scopus_id/85187255253
url http://hdl.handle.net/10261/365886
https://api.elsevier.com/content/abstract/scopus_id/85187255253
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI//PRE2021–096909
Tropical medicine and infectious disease
http://dx.doi.org/doi.org/10.3390/tropicalmed9020030
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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