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dc.creatorBonilla‑Ramírez, L. (Leonardo)-
dc.creatorGaliano, S. (Silvia)-
dc.creatorQuiliano, M. (Miguel)-
dc.creatorAldana, I. (Ignacio)-
dc.creatorPabon, A. (Adriana)-
dc.date.accessioned2022-06-09T12:04:24Z-
dc.date.available2022-06-09T12:04:24Z-
dc.date.issued2019-
dc.identifier.citationBonilla‑Ramírez, L. (Leonardo); Galiano, S. (Silvia); Quiliano, M. (Miguel); et al. "Primaquine–quinoxaline 1,4‑di‑N‑oxide hybrids with action on the exo‑erythrocytic forms of Plasmodium induce their efect by the production of reactive oxygen species". Malaria Journal. 18 (201), 2019,es
dc.identifier.issn1475-2875-
dc.identifier.uri10.1186/s12936-019-2825-8-
dc.identifier.urihttps://hdl.handle.net/10171/63629-
dc.description.abstractBackground: The challenge in anti-malarial chemotherapy is based on the emergence of resistance to drugs and the search for medicines against all stages of the life cycle of Plasmodium spp. as a therapeutic target. Nowadays, many molecules with anti-malarial activity are reported. However, few studies about the cellular and molecular mechanisms to understand their mode of action have been explored. Recently, new primaquine-based hybrids as new molecules with potential multi-acting anti-malarial activity were reported and two hybrids of primaquine linked to quinoxaline 1,4-di-N-oxide (PQ–QdNO) were identifed as the most active against erythrocytic, exoerythrocytic and sporogonic stages. Methods: To further understand the anti-malarial mode of action (MA) of these hybrids, hepg2-CD81 were infected with Plasmodium yoelii 17XNL and treated with PQ–QdNO hybrids during 48 h. After were evaluated the production of ROS, the mitochondrial depolarization, the total glutathione content, the DNA damage and proteins related to oxidative stress and death cell. Results: In a preliminary analysis as tissue schizonticidals, these hybrids showed a mode of action dependent on peroxides production, but independent of the activation of transcription factor p53, mitochondrial depolarization and arrest cell cycle. Conclusions: Primaquine–quinoxaline 1,4-di-N-oxide hybrids exert their antiplasmodial activity in the exoeryth‑ rocytic phase by generating high levels of oxidative stress which promotes the increase of total glutathione levels, through oxidation stress sensor protein DJ-1. In addition, the role of HIF1a in the mode of action of quinoxaline 1,4-diN-oxide is independent of biological activity.es_ES
dc.description.sponsorshipThis work was supported by Colciencias Grant #111571249992 (contract RC-377-2016), PIUNA Project-University of Navarra and Foundation CAN (Grant number: 70391). L. B-R. was funded by Colciencias Grants (528-2011) and M.Q is grateful to “Programa Nacional de Innovación para la competitividad y productividad” (Innóvate-Perú) for his Ph. D. scholarship (Grant 065-FINCYTBDE-2014). The authors are the Institute of Tropical Health (ISTUN) of University of Navarra for the financial support and helpes_ES
dc.language.isoenges_ES
dc.publisherSpringer Science and Business Media LLCes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectMalariaes_ES
dc.subjectPlasmodiumes_ES
dc.subjectExoerythrocytic stagees_ES
dc.subjectQuinoxaline 1es_ES
dc.subject4-Di-N-oxidees_ES
dc.subjectCell deathes_ES
dc.subjectOxide stresses_ES
dc.titlePrimaquine–quinoxaline 1,4‑di‑N‑oxide hybrids with action on the exo‑erythrocytic forms of Plasmodium induce their efect by the production of reactive oxygen specieses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.description.noteThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.es_ES
dadun.citation.number201es_ES
dadun.citation.publicationNameMalaria Journales_ES
dadun.citation.volume18es_ES

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