{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T08:26:17Z","timestamp":1761294377193,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Primary amoebic encephalitis (PAM) caused by the opportunistic pathogen Naegleria fowleri is characterized as a rapid and lethal infection of the brain which ends in the death of the patient in more than 90% of the reported cases. This amoeba thrives in warm water bodies and causes infection after individuals perform risky activities such as splashing or diving, mostly in non-treated water bodies such as lakes and ponds. Moreover, the infection progresses very fast and no fully effective molecules have currently been found to treat PAM. In this study, naphthyridines fused with chromenes or chromenones previously synthetized by the group were tested in vitro against the trophozoite stage of two strains of N. fowleri. In addition, the most active molecule was evaluated in order to check the induction of programmed cell death (PCD) in the treated amoebae. Compound 3 showed good anti-Naegleria activity (61.45 \u00b1 5.27 and 76.61 \u00b1 10.84 \u00b5M, respectively) against the two different strains (ATCC\u00ae 30808 and ATCC\u00ae 30215) and a good selectivity compared to the cytotoxicity values (&gt;300 \u00b5M). In addition, it was able to induce PCD, causing DNA condensation, damage at the cellular membrane, reduction in mitochondrial membrane potential and ATP levels, and ROS generation. Hence, naphthyridines fused with chromenes or chromenones could be potential therapeutic agents against PAM in the near future.<\/jats:p>","DOI":"10.3390\/ph14101013","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T21:26:20Z","timestamp":1633728380000},"page":"1013","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Naphthyridine Derivatives Induce Programmed Cell Death in Naegleria fowleri"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8313-0219","authenticated-orcid":false,"given":"Aitor","family":"Rizo-Liendo","sequence":"first","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda, Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38203 La Laguna, Spain"},{"name":"Departamento de Obstetricia, Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna, 38203 La Laguna, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I\u00f1igo","family":"Arberas-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda, Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38203 La Laguna, Spain"},{"name":"Departamento de Obstetricia, Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna, 38203 La Laguna, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Endika","family":"Martin-Encinas","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica I, Facultad de Farmacia and Centro de Investigaci\u00f3n Lascaray (Lascaray Research Center), Universidad del Pa\u00eds Vasco\/Euskal Herriko Unibertsitatea (UPV\/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ines","family":"Sifaoui","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda, Astrof\u00edsico Fco. 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S\u00e1nchez, S\/N, 38203 La Laguna, Spain"},{"name":"Departamento de Obstetricia, Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna, 38203 La Laguna, Spain"},{"name":"Red de Investigaci\u00f3n Colaborativa en Enfermedades Tropicales (RICET), 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Chao-Pellicer","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda, Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38203 La Laguna, Spain"},{"name":"Departamento de Obstetricia, Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna, 38203 La Laguna, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 and Centro de Investigaci\u00f3n Lascaray (Lascaray Research Center), Universidad del Pa\u00eds Vasco\/Euskal Herriko Unibertsitatea (UPV\/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6365-0324","authenticated-orcid":false,"given":"Francisco","family":"Palacios","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica I, Facultad de Farmacia and Centro de Investigaci\u00f3n Lascaray (Lascaray Research Center), Universidad del Pa\u00eds Vasco\/Euskal Herriko Unibertsitatea (UPV\/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6233-8224","authenticated-orcid":false,"given":"Jos\u00e9 E.","family":"Pi\u00f1ero","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda, Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38203 La Laguna, Spain"},{"name":"Departamento de Obstetricia, Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna, 38203 La Laguna, Spain"},{"name":"Red de Investigaci\u00f3n Colaborativa en Enfermedades Tropicales (RICET), 28006 Madrid, Spain"},{"name":"Consorcio Centro de Investigacion Biomedica En Red M.P. (CIBER) de Enfermedades Infecciosas, Inst. de Salud Carlos III, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Lorenzo-Morales","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda, Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38203 La Laguna, Spain"},{"name":"Departamento de Obstetricia, Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna, 38203 La Laguna, Spain"},{"name":"Red de Investigaci\u00f3n Colaborativa en Enfermedades Tropicales (RICET), 28006 Madrid, Spain"},{"name":"Consorcio Centro de Investigacion Biomedica En Red M.P. (CIBER) de Enfermedades Infecciosas, Inst. de Salud Carlos III, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tillery, L., Barrett, K., Goldstein, J., Lassner, J.W., Osterhout, B., Tran, N.L., Xu, L., Young, R.M., Craig, J., and Chun, I. (2021). Naegleria fowleri: Protein structures to facilitate drug discovery for the deadly, pathogenic free-living amoeba. 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