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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.<\/jats:p>","DOI":"10.3390\/molecules29010074","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T04:44:40Z","timestamp":1703220280000},"page":"74","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9663-060X","authenticated-orcid":false,"given":"Estela","family":"Melc\u00f3n-Fernandez","sequence":"first","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Endika","family":"Mart\u00edn-Encinas","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica I, Facultad de Farmacia, Lascaray Research Center, Universidad del Pa\u00eds Vasco\/Euskal Herriko Unibertsitatea (UPV\/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Palacios","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica I, Facultad de Farmacia, Lascaray Research Center, Universidad del Pa\u00eds Vasco\/Euskal Herriko Unibertsitatea (UPV\/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6854-5507","authenticated-orcid":false,"given":"Gulio","family":"Galli","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 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":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3723-1895","authenticated-orcid":false,"given":"Mar\u00eda","family":"Mart\u00ednez-Valladares","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 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":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0866-3493","authenticated-orcid":false,"given":"Concepci\u00f3n","family":"Alonso","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica I, Facultad de Farmacia, Lascaray Research Center, Universidad del Pa\u00eds Vasco\/Euskal Herriko Unibertsitatea (UPV\/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"P\u00e9rez-Pertejo","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,22]]},"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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