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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\u2014a nitrofurantoin used against vaginal infections\u2014as a promising repurposing drug against a mouse model of visceral leishmaniasis. In the present work, we have tested combinations of miltefosine\u2014the only oral drug currently used against leishmaniasis\u2014with 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.<\/jats:p>","DOI":"10.3390\/ijms24021635","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T02:04:45Z","timestamp":1673834685000},"page":"1635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Miltefosine and Nifuratel Combination: A Promising Therapy for the Treatment of Leishmania donovani Visceral Leishmaniasis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9663-060X","authenticated-orcid":false,"given":"Estela","family":"Melcon-Fernandez","sequence":"first","affiliation":[{"name":"Department Ciencias Biom\u00e9dicas, Universidad de Le\u00f3n, Campus de Vegazana s\/n P.C, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6854-5507","authenticated-orcid":false,"given":"Giulio","family":"Galli","sequence":"additional","affiliation":[{"name":"Department Ciencias Biom\u00e9dicas, Universidad de Le\u00f3n, Campus de Vegazana s\/n P.C, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5617-9669","authenticated-orcid":false,"given":"Carlos","family":"Garc\u00eda-Estrada","sequence":"additional","affiliation":[{"name":"Department Ciencias Biom\u00e9dicas, Universidad de Le\u00f3n, Campus de Vegazana s\/n P.C, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0418-6116","authenticated-orcid":false,"given":"Rafael","family":"Bala\u00f1a-Fouce","sequence":"additional","affiliation":[{"name":"Department Ciencias Biom\u00e9dicas, Universidad de Le\u00f3n, Campus de Vegazana s\/n P.C, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9148-2997","authenticated-orcid":false,"given":"Rosa M.","family":"Reguera","sequence":"additional","affiliation":[{"name":"Department Ciencias Biom\u00e9dicas, Universidad de Le\u00f3n, Campus de Vegazana s\/n P.C, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"P\u00e9rez-Pertejo","sequence":"additional","affiliation":[{"name":"Department Ciencias Biom\u00e9dicas, Universidad de Le\u00f3n, Campus de Vegazana s\/n P.C, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1007\/s00436-021-07139-2","article-title":"Leishmaniasis: Where are we and where are we heading?","volume":"120","author":"Sasidharan","year":"2021","journal-title":"Parasitol. 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