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,...
| Autores: | , , , , , , , , |
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| 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 |
| Sumario: | [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. |
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