Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines

[EN]In the absence of a vaccine, there is a need to find new drugs for the treatment of neglected tropical diseases, such as leishmaniasis, that can overcome the many drawbacks of those currently used. These disadvantages include cost, the need to maintain a cold chain, the route of administration,...

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Autores: Melcón Fernández, Estela, Martín Encinas, Endika, Palacios, Francisco, Galli, Giulio, Reguera Torres, Rosa María, Martínez Valladares, María, Balaña Fouce, Rafael, Alonso, Concepción, Pérez Pertejo, Maria Yolanda
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de León
Repositorio:BULERIA. Repositorio Institucional de la Universidad de León
OAI Identifier:oai:buleria.unileon.es:10612/25700
Acceso en línea:https://www.mdpi.com/1420-3049/29/1/74
https://hdl.handle.net/10612/25700
Access Level:acceso abierto
Palabra clave:Producción animal
Toxicología
Visceral leishmaniasis
Fused 1,5-naphthyridines
Fused 1,8-naphthyridines
Intramacrophagic Leishmania parasites
Mouse intestinal organoids
2401.12 Parasitología Animal
3207.12 Parasitología
3209 Farmacología
3104 Producción Animal
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spelling Antileishmanial Effect of 1,5- and 1,8-Substituted Fused NaphthyridinesMelcón Fernández, EstelaMartín Encinas, EndikaPalacios, FranciscoGalli, GiulioReguera Torres, Rosa MaríaMartínez Valladares, MaríaBalaña Fouce, RafaelAlonso, ConcepciónPérez Pertejo, Maria YolandaProducción animalToxicologíaVisceral leishmaniasisFused 1,5-naphthyridinesFused 1,8-naphthyridinesIntramacrophagic Leishmania parasitesMouse intestinal organoids2401.12 Parasitología Animal3207.12 Parasitología3209 Farmacología3104 Producción Animal[EN]In the absence of a vaccine, there is a need to find new drugs for the treatment of neglected tropical diseases, such as leishmaniasis, that can overcome the many drawbacks of those currently used. These disadvantages include cost, the need to maintain a cold chain, the route of administration, the associated adverse effects and the generation of resistance. In this work we have evaluated the antileishmanial effect of 1,5- and 1,8-substituted fused naphthyridines through in vitro and ex vivo assays, using genetically modified axenic and intramacrophagic Leishmania infantum amastigotes. The toxicity of these compounds has been tested in the mammalian host cell using murine splenic macrophages, as well as in murine intestinal organoids (miniguts) in order to assess their potential for oral administration. The 1,8- derivatives showed greater leishmanicidal activity and the presence of a nitrogen atom in the fused ring to the naphthyridine was important to increase the activity of both types of molecules. The aromatization of the pyridine ring also had marked differences in the activity of the compounds.SIFinancial support from Grant PID2021-122558OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by the “European Union”; Basque Government (GV, IT1701-22) and Vital Foundation (VITAL23/28) is gratefully acknowledged. G.G. is supported by Grant PRE2021-096909 funded by MCIN/AEI/10.13039/501100011033 and, by “ESF Investing in your future” is gratefully acknowledged.MDPIToxicologiaFacultad de Veterinaria2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://www.mdpi.com/1420-3049/29/1/74https://hdl.handle.net/10612/25700reponame:BULERIA. Repositorio Institucional de la Universidad de Leóninstname:Universidad de LeónEspañolinfo:eu-repo/grantAgreement/AEI/Programa Estatal para Impulsar la Investigación Científico-Técnica y su Transferencia/PID2021-122558OB-I00http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:buleria.unileon.es:10612/257002026-06-24T12:43:27Z
dc.title.none.fl_str_mv Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines
title Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines
spellingShingle Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines
Melcón Fernández, Estela
Producción animal
Toxicología
Visceral leishmaniasis
Fused 1,5-naphthyridines
Fused 1,8-naphthyridines
Intramacrophagic Leishmania parasites
Mouse intestinal organoids
2401.12 Parasitología Animal
3207.12 Parasitología
3209 Farmacología
3104 Producción Animal
title_short Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines
title_full Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines
title_fullStr Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines
title_full_unstemmed Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines
title_sort Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines
dc.creator.none.fl_str_mv Melcón Fernández, Estela
Martín Encinas, Endika
Palacios, Francisco
Galli, Giulio
Reguera Torres, Rosa María
Martínez Valladares, María
Balaña Fouce, Rafael
Alonso, Concepción
Pérez Pertejo, Maria Yolanda
author Melcón Fernández, Estela
author_facet Melcón Fernández, Estela
Martín Encinas, Endika
Palacios, Francisco
Galli, Giulio
Reguera Torres, Rosa María
Martínez Valladares, María
Balaña Fouce, Rafael
Alonso, Concepción
Pérez Pertejo, Maria Yolanda
author_role author
author2 Martín Encinas, Endika
Palacios, Francisco
Galli, Giulio
Reguera Torres, Rosa María
Martínez Valladares, María
Balaña Fouce, Rafael
Alonso, Concepción
Pérez Pertejo, Maria Yolanda
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Toxicologia
Facultad de Veterinaria
dc.subject.none.fl_str_mv Producción animal
Toxicología
Visceral leishmaniasis
Fused 1,5-naphthyridines
Fused 1,8-naphthyridines
Intramacrophagic Leishmania parasites
Mouse intestinal organoids
2401.12 Parasitología Animal
3207.12 Parasitología
3209 Farmacología
3104 Producción Animal
topic Producción animal
Toxicología
Visceral leishmaniasis
Fused 1,5-naphthyridines
Fused 1,8-naphthyridines
Intramacrophagic Leishmania parasites
Mouse intestinal organoids
2401.12 Parasitología Animal
3207.12 Parasitología
3209 Farmacología
3104 Producción Animal
description [EN]In the absence of a vaccine, there is a need to find new drugs for the treatment of neglected tropical diseases, such as leishmaniasis, that can overcome the many drawbacks of those currently used. These disadvantages include cost, the need to maintain a cold chain, the route of administration, the associated adverse effects and the generation of resistance. In this work we have evaluated the antileishmanial effect of 1,5- and 1,8-substituted fused naphthyridines through in vitro and ex vivo assays, using genetically modified axenic and intramacrophagic Leishmania infantum amastigotes. The toxicity of these compounds has been tested in the mammalian host cell using murine splenic macrophages, as well as in murine intestinal organoids (miniguts) in order to assess their potential for oral administration. The 1,8- derivatives showed greater leishmanicidal activity and the presence of a nitrogen atom in the fused ring to the naphthyridine was important to increase the activity of both types of molecules. The aromatization of the pyridine ring also had marked differences in the activity of the compounds.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://www.mdpi.com/1420-3049/29/1/74
https://hdl.handle.net/10612/25700
url https://www.mdpi.com/1420-3049/29/1/74
https://hdl.handle.net/10612/25700
dc.language.none.fl_str_mv Español
language_invalid_str_mv Español
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/AEI/Programa Estatal para Impulsar la Investigación Científico-Técnica y su Transferencia/PID2021-122558OB-I00
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:BULERIA. Repositorio Institucional de la Universidad de León
instname:Universidad de León
instname_str Universidad de León
reponame_str BULERIA. Repositorio Institucional de la Universidad de León
collection BULERIA. Repositorio Institucional de la Universidad de León
repository.name.fl_str_mv
repository.mail.fl_str_mv
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