{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:42:31Z","timestamp":1792687351564,"version":"4.5.0"},"reference-count":62,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:00:00Z","timestamp":1724630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Le\u00f3n"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Leishmania infantum is the vector-borne trypanosomatid parasite causing visceral leishmaniasis in the Mediterranean basin. This neglected tropical disease is treated with a limited number of obsolete drugs that are not exempt from adverse effects and whose overuse has promoted the emergence of resistant pathogens. In the search for novel antitrypanosomatid molecules that help overcome these drawbacks, drug repurposing has emerged as a good strategy. Nitroaromatic compounds have been found in drug discovery campaigns as promising antileishmanial molecules. Fexinidazole (recently introduced for the treatment of stages 1 and 2 of African trypanosomiasis), and pretomanid, which share the nitroimidazole nitroaromatic structure, have provided antileishmanial activity in different studies. In this work, we have tested the in vitro efficacy of these two nitroimidazoles to validate our 384-well high-throughput screening (HTS) platform consisting of L. infantum parasites emitting the near-infrared fluorescent protein (iRFP) as a biomarker of cell viability. These molecules showed good efficacy in both axenic and intramacrophage amastigotes and were poorly cytotoxic in RAW 264.7 and HepG2 cultures. Fexinidazole and pretomanid induced the production of ROS in axenic amastigotes but were not able to inhibit trypanothione reductase (TryR), thus suggesting that these compounds may target thiol metabolism through a different mechanism of action.<\/jats:p>","DOI":"10.3390\/molecules29174041","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T10:01:51Z","timestamp":1724666511000},"page":"4041","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Free Radical Production Induced by Nitroimidazole Compounds Lead to Cell Death in Leishmania infantum Amastigotes"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7191-6007","authenticated-orcid":false,"given":"Julia","family":"Andr\u00e9s-Rodr\u00edguez","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"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1069-3940","authenticated-orcid":false,"given":"Mar\u00eda-Cristina","family":"Gonz\u00e1lez-Montero","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\/0009-0004-5177-293X","authenticated-orcid":false,"given":"Nerea","family":"Garc\u00eda-Fern\u00e1ndez","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\/0000-0001-7509-7204","authenticated-orcid":false,"given":"Estefan\u00eda","family":"Calvo-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda-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"},{"name":"Instituto de Biomedicina (IBIOMED), 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-Mar\u00eda","family":"Reguera-Torres","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"},{"name":"Instituto de Biomedicina (IBIOMED), 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"},{"name":"Instituto de Biomedicina (IBIOMED), Universidad de Le\u00f3n, Campus de Vegazana s\/n, 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":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"},{"name":"Instituto de Biomedicina (IBIOMED), Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,26]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024, July 22). 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