Miltefosine and nifuratel combination: a promising therapy for the treatment of leishmania donovani visceral leishmaniasis

[EN] Visceral leishmaniasis is a neglected vector-borne tropical disease caused by Leishmania donovani and Leishmania infantum that is endemic not only in East African countries, but also in Asia, regions of South America and the Mediterranean Basin. For the pharmacological control of this disease,...

Descripción completa

Detalles Bibliográficos
Autores: Melcón Fernández, Estela, Galli, Giulio, García Estrada, Carlos, Balaña Fouce, Rafael, Reguera Torres, Rosa María, Pérez Pertejo, Maria Yolanda
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad Rey Juan Carlos
Repositorio:BULERIA. Repositorio Institucional de la Universidad de León
OAI Identifier:oai:buleria.unileon.es:10612/17821
Acceso en línea:https://www.mdpi.com/1422-0067/24/2/1635
https://hdl.handle.net/10612/17821
Access Level:acceso abierto
Palabra clave:Farmacología
Medicina. Salud
Leishmania
Drug combinations
Nifuratel
Miltefosine
Drug repurposing
32 Ciencias Médicas
3214 Toxicología
3109 Ciencias Veterinarias
id ES_f8d321bbec75845fabb4680e29a71a10
oai_identifier_str oai:buleria.unileon.es:10612/17821
network_acronym_str ES
network_name_str España
repository_id_str
spelling Miltefosine and nifuratel combination: a promising therapy for the treatment of leishmania donovani visceral leishmaniasisMelcón Fernández, EstelaGalli, GiulioGarcía Estrada, CarlosBalaña Fouce, RafaelReguera Torres, Rosa MaríaPérez Pertejo, Maria YolandaFarmacologíaMedicina. SaludLeishmaniaDrug combinationsNifuratelMiltefosineDrug repurposing32 Ciencias Médicas3214 Toxicología3109 Ciencias Veterinarias[EN] Visceral leishmaniasis is a neglected vector-borne tropical disease caused by Leishmania donovani and Leishmania infantum that is endemic not only in East African countries, but also in Asia, regions of South America and the Mediterranean Basin. For the pharmacological control of this disease, there is a limited number of old and, in general, poorly adherent drugs, with a multitude of adverse effects and low oral bioavailability, which favor the emergence of resistant pathogens. Pentavalent antimonials are the first-line drugs, but due to their misuse, resistant Leishmania strains have emerged worldwide. Although these drugs have saved many lives, it is recommended to reduce their use as much as possible and replace them with novel and more friendly drugs. From a commercial collection of anti-infective drugs, we have recently identified nifuratel-a nitrofurantoin used against vaginal infections-as a promising repurposing drug against a mouse model of visceral leishmaniasis. In the present work, we have tested combinations of miltefosine-the only oral drug currently used against leishmaniasis-with nifuratel in different proportions, both in axenic amastigotes from bone marrow and in intracellular amastigotes from infected Balb/c mouse spleen macrophages, finding a potent synergy in both cases. In vivo evaluation of oral miltefosine/nifuratel combinations using a bioimaging platform has revealed the potential of these combinations for the treatment of this disease.SIThis research was partially funded by MINECO; SAF2017-83575-R and PID 2020-119031RB-100 to R.M.R. E.M.-F. is contracted with EU PRIMA (PCI2022-132925); G.G. is recipient of FPI scholarship (PRE 2021 096909) supported by AEIMDPIToxicologiaFacultad de Veterinaria2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://www.mdpi.com/1422-0067/24/2/1635https://hdl.handle.net/10612/17821reponame:BULERIA. Repositorio Institucional de la Universidad de Leóninstname:Universidad Rey Juan CarlosInglésinfo:eu-repo/grantAgreement/AEI/ Programa Estatal de I+D+i Orientada a los Retos de la Sociedad / SAF2017-83575-R http://creativecommons.org/licenses/by-nc-nd/3.0/info:eu-repo/semantics/openAccessoai:buleria.unileon.es:10612/178212026-06-24T12:43:27Z
dc.title.none.fl_str_mv Miltefosine and nifuratel combination: a promising therapy for the treatment of leishmania donovani visceral leishmaniasis
title Miltefosine and nifuratel combination: a promising therapy for the treatment of leishmania donovani visceral leishmaniasis
spellingShingle Miltefosine and nifuratel combination: a promising therapy for the treatment of leishmania donovani visceral leishmaniasis
Melcón Fernández, Estela
Farmacología
Medicina. Salud
Leishmania
Drug combinations
Nifuratel
Miltefosine
Drug repurposing
32 Ciencias Médicas
3214 Toxicología
3109 Ciencias Veterinarias
title_short Miltefosine and nifuratel combination: a promising therapy for the treatment of leishmania donovani visceral leishmaniasis
title_full Miltefosine and nifuratel combination: a promising therapy for the treatment of leishmania donovani visceral leishmaniasis
title_fullStr Miltefosine and nifuratel combination: a promising therapy for the treatment of leishmania donovani visceral leishmaniasis
title_full_unstemmed Miltefosine and nifuratel combination: a promising therapy for the treatment of leishmania donovani visceral leishmaniasis
title_sort Miltefosine and nifuratel combination: a promising therapy for the treatment of leishmania donovani visceral leishmaniasis
dc.creator.none.fl_str_mv Melcón Fernández, Estela
Galli, Giulio
García Estrada, Carlos
Balaña Fouce, Rafael
Reguera Torres, Rosa María
Pérez Pertejo, Maria Yolanda
author Melcón Fernández, Estela
author_facet Melcón Fernández, Estela
Galli, Giulio
García Estrada, Carlos
Balaña Fouce, Rafael
Reguera Torres, Rosa María
Pérez Pertejo, Maria Yolanda
author_role author
author2 Galli, Giulio
García Estrada, Carlos
Balaña Fouce, Rafael
Reguera Torres, Rosa María
Pérez Pertejo, Maria Yolanda
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Toxicologia
Facultad de Veterinaria
dc.subject.none.fl_str_mv Farmacología
Medicina. Salud
Leishmania
Drug combinations
Nifuratel
Miltefosine
Drug repurposing
32 Ciencias Médicas
3214 Toxicología
3109 Ciencias Veterinarias
topic Farmacología
Medicina. Salud
Leishmania
Drug combinations
Nifuratel
Miltefosine
Drug repurposing
32 Ciencias Médicas
3214 Toxicología
3109 Ciencias Veterinarias
description [EN] Visceral leishmaniasis is a neglected vector-borne tropical disease caused by Leishmania donovani and Leishmania infantum that is endemic not only in East African countries, but also in Asia, regions of South America and the Mediterranean Basin. For the pharmacological control of this disease, there is a limited number of old and, in general, poorly adherent drugs, with a multitude of adverse effects and low oral bioavailability, which favor the emergence of resistant pathogens. Pentavalent antimonials are the first-line drugs, but due to their misuse, resistant Leishmania strains have emerged worldwide. Although these drugs have saved many lives, it is recommended to reduce their use as much as possible and replace them with novel and more friendly drugs. From a commercial collection of anti-infective drugs, we have recently identified nifuratel-a nitrofurantoin used against vaginal infections-as a promising repurposing drug against a mouse model of visceral leishmaniasis. In the present work, we have tested combinations of miltefosine-the only oral drug currently used against leishmaniasis-with nifuratel in different proportions, both in axenic amastigotes from bone marrow and in intracellular amastigotes from infected Balb/c mouse spleen macrophages, finding a potent synergy in both cases. In vivo evaluation of oral miltefosine/nifuratel combinations using a bioimaging platform has revealed the potential of these combinations for the treatment of this disease.
publishDate 2023
dc.date.none.fl_str_mv 2023
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/1422-0067/24/2/1635
https://hdl.handle.net/10612/17821
url https://www.mdpi.com/1422-0067/24/2/1635
https://hdl.handle.net/10612/17821
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/AEI/ Programa Estatal de I+D+i Orientada a los Retos de la Sociedad / SAF2017-83575-R
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/
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 Rey Juan Carlos
instname_str Universidad Rey Juan Carlos
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
_version_ 1869425037706002432
score 15,300719

Similares en LA Referencia