{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T08:28:03Z","timestamp":1761294483909,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Spanish Ministry of Science, Innovation and Universities and the Spanish State Research Agency","award":["RTI2018-094579-B-I00","2017-SGR-908","USP-05-2019"],"award-info":[{"award-number":["RTI2018-094579-B-I00","2017-SGR-908","USP-05-2019"]}]},{"DOI":"10.13039\/501100002809","name":"the Generalitat de Catalunya, Spain","doi-asserted-by":"publisher","award":["RTI2018-094579-B-I00","2017-SGR-908","USP-05-2019"],"award-info":[{"award-number":["RTI2018-094579-B-I00","2017-SGR-908","USP-05-2019"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Uni\u00f3n Iberoamericana de Universidades","award":["RTI2018-094579-B-I00","2017-SGR-908","USP-05-2019"],"award-info":[{"award-number":["RTI2018-094579-B-I00","2017-SGR-908","USP-05-2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The evolution of resistance by the malaria parasite to artemisinin, the key component of the combination therapy strategies that are at the core of current antimalarial treatments, calls for the urgent identification of new fast-acting antimalarials. The apicoplast organelle is a preferred target of antimalarial drugs because it contains biochemical processes absent from the human host. Fosmidomycin is the only drug in clinical trials targeting the apicoplast, where it inhibits the methyl erythritol phosphate (MEP) pathway. Here, we characterized the antiplasmodial activity of domiphen bromide (DB), another MEP pathway inhibitor with a rapid mode of action that arrests the in vitro growth of Plasmodium falciparum at the early trophozoite stage. Metabolomic analysis of the MEP pathway and Krebs cycle intermediates in 20 \u00b5M DB-treated parasites suggested a rapid activation of glycolysis with a concomitant decrease in mitochondrial activity, consistent with a rapid killing of the pathogen. These results present DB as a model compound for the development of new, potentially interesting drugs for future antimalarial combination therapies.<\/jats:p>","DOI":"10.3390\/pharmaceutics14071320","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T23:11:19Z","timestamp":1655939479000},"page":"1320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Characterization of Domiphen Bromide as a New Fast-Acting Antiplasmodial Agent Inhibiting the Apicoplastidic Methyl Erythritol Phosphate Pathway"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3047-8991","authenticated-orcid":false,"given":"Arnau","family":"Biosca","sequence":"first","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal, Hospital Cl\u00ednic-Universitat de Barcelona), Rossell\u00f3 149-153, 08036 Barcelona, Spain"},{"name":"Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, 08028 Barcelona, Spain"},{"name":"Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Mart\u00ed i Franqu\u00e8s 1, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal, Hospital Cl\u00ednic-Universitat de Barcelona), Rossell\u00f3 149-153, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8172-1827","authenticated-orcid":false,"given":"Alex","family":"Gomez-Gomez","sequence":"additional","affiliation":[{"name":"Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program, IMIM-Institut Hospital del Mar d\u2019Investigacions M\u00e8diques, Doctor Aiguader 88, 08003 Barcelona, Spain"},{"name":"Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aritz","family":"Lafuente","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal, Hospital Cl\u00ednic-Universitat de Barcelona), Rossell\u00f3 149-153, 08036 Barcelona, Spain"},{"name":"Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, 08028 Barcelona, Spain"},{"name":"Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Mart\u00ed i Franqu\u00e8s 1, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6133-0869","authenticated-orcid":false,"given":"Valent\u00edn","family":"Iglesias","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal, Hospital Cl\u00ednic-Universitat de Barcelona), Rossell\u00f3 149-153, 08036 Barcelona, Spain"},{"name":"Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, 08028 Barcelona, Spain"},{"name":"Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Mart\u00ed i Franqu\u00e8s 1, 08028 Barcelona, Spain"},{"name":"Institut de Biotecnologia i Biomedicina and Departament de Bioqu\u00edmica i Biologia Molecular, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1735-9728","authenticated-orcid":false,"given":"Oscar J.","family":"Pozo","sequence":"additional","affiliation":[{"name":"Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program, IMIM-Institut Hospital del Mar d\u2019Investigacions M\u00e8diques, Doctor Aiguader 88, 08003 Barcelona, Spain"},{"name":"Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8749-1428","authenticated-orcid":false,"given":"Santiago","family":"Imperial","sequence":"additional","affiliation":[{"name":"Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Mart\u00ed i Franqu\u00e8s 1, 08028 Barcelona, Spain"},{"name":"Department of Biochemistry and Molecular Biomedicine, University of Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4622-9631","authenticated-orcid":false,"given":"Xavier","family":"Fern\u00e0ndez-Busquets","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal, Hospital Cl\u00ednic-Universitat de Barcelona), Rossell\u00f3 149-153, 08036 Barcelona, Spain"},{"name":"Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, 08028 Barcelona, Spain"},{"name":"Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Mart\u00ed i Franqu\u00e8s 1, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022, June 18). 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