Naphthyridine Derivatives Induce Programmed Cell Death in Naegleria fowleri
dc.contributor.author | Rizo-Liendo, Aitor | |
dc.contributor.author | Arberas-Jiménez, Iñigo | |
dc.contributor.author | Martín Encinas, Endika | |
dc.contributor.author | Sifaoui, Ines | |
dc.contributor.author | Reyes-Batlle, María | |
dc.contributor.author | Chao-Pellicer, Javier | |
dc.contributor.author | Alonso Pérez, Concepción Estibaliz | |
dc.contributor.author | Palacios Gambra, Francisco Javier | |
dc.contributor.author | Piñero, José E. | |
dc.contributor.author | Lorenzo-Morales, Jacob | |
dc.date.accessioned | 2021-10-27T08:33:10Z | |
dc.date.available | 2021-10-27T08:33:10Z | |
dc.date.issued | 2021-10-01 | |
dc.identifier.citation | Pharmaceuticals 14(10) : (2021) // Article ID 1013 | es_ES |
dc.identifier.issn | 1424-8247 | |
dc.identifier.uri | http://hdl.handle.net/10810/53641 | |
dc.description.abstract | 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 ± 5.27 and 76.61 ± 10.84 µM, respectively) against the two different strains (ATCC® 30808 and ATCC® 30215) and a good selectivity compared to the cytotoxicity values (>300 µM). 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. | es_ES |
dc.description.sponsorship | This work was funded by PI18/01380 from the Instituto de Salud Carlos III, Spain; RICET (project RD16/0027/0001) from the Programa Redes Temáticas de Investigación Cooperativa, FIS (Ministerio Español de Salud, Madrid, Spain); and CB21/13/00100 Consorcio Centro De Investigacion Biomedica En Red M.P. (CIBER) de Enfermedades Infecciosas, Inst. de Salud Carlos III, Madrid, Spain. A.R.L. and I.A.J. were funded by the Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI). Additionally, financial support from the Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI), and Fondo Europeo de Desarrollo Regional (FEDER; RTI2018-101818-B-I00, UE) and from Gobierno Vasco, Universidad del País Vasco (GV, IT 992-16; UPV) is gratefully acknowledged. Technical and human support provided by IZO-SGI, SGIker (UPV/EHU, MICINN, GV/EJ, ERDF, and ESF) is gratefully acknowledged. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/ RTI2018-101818-B-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | |
dc.subject | Naegleria fowleri | es_ES |
dc.subject | meningoencephalitis | es_ES |
dc.subject | naphthyridine derivatives | es_ES |
dc.subject | programmed cell death | es_ES |
dc.title | Naphthyridine Derivatives Induce Programmed Cell Death in Naegleria fowleri | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2021-10-22T13:55:59Z | |
dc.rights.holder | 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/1424-8247/14/10/1013/htm | es_ES |
dc.identifier.doi | 10.3390/ph14101013 | |
dc.departamentoes | Química orgánica I | |
dc.departamentoeu | Kimika organikoa I |
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Except where otherwise noted, this item's license is described as 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).