{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:32:43Z","timestamp":1791311563294,"version":"4.3.1"},"reference-count":59,"publisher":"SAGE Publications","issue":"15","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    Early phagocytosis of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes parasitized by\n                    <jats:italic toggle=\"yes\">Plasmodium falciparum<\/jats:italic>\n                    were shown to protect G6PD-deficient populations from severe malaria. Here, we investigated the mechanism of a novel antimalarial series, namely 3-[substituted-benzyl]-menadiones, to understand whether these NADPH-consuming redox-cyclers, which induce oxidative stress, mimic the natural protection of G6PD deficiency.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    We demonstrated that the key benzoylmenadione metabolite of the lead compound acts as an efficient redox-cycler in NADPH-dependent methaemoglobin reduction, leading to the continuous formation of reactive oxygen species, ferrylhaemoglobin, and subsequent haemichrome precipitation. Structure\u2013activity relationships evidenced that both drug metabolites and haemoglobin catabolites contribute to potentiate drug effects and inhibit parasite development. Disruption of redox homeostasis by the lead benzylmenadione was specifically induced in\n                    <jats:italic toggle=\"yes\">Plasmodium falciparum<\/jats:italic>\n                    parasitized erythrocytes and not in non-infected cells, and was visualized\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    changes in the glutathione redox potential of living parasite cytosols. Furthermore, the redox-cycler shows additive and synergistic effects in combination with compounds affecting the NADPH flux\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    .\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    The lead benzylmenadione\n                    <jats:bold>1c<\/jats:bold>\n                    is the first example of a novel redox-active agent that mimics the behavior of a\n                    <jats:italic toggle=\"yes\">falciparum<\/jats:italic>\n                    parasite developing inside a G6PD-deficient red blood cell (RBC) giving rise to malaria protection, and it exerts specific additive effects that are inhibitory to parasite development, without harm for non-infected G6PD-sufficient or -deficient RBCs.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    <\/jats:bold>\n                    This strategy offers an innovative perspective for the development of future antimalarial drugs for G6PD-sufficient and -deficient populations.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    22, 1337\u20131352.\n                  <\/jats:p>","DOI":"10.1089\/ars.2014.6047","type":"journal-article","created":{"date-parts":[[2015,2,25]],"date-time":"2015-02-25T12:04:14Z","timestamp":1424865854000},"page":"1337-1351","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":42,"title":["Antimalarial NADPH-Consuming Redox-Cyclers As Superior Glucose-6-Phosphate Dehydrogenase Deficiency Copycats"],"prefix":"10.1177","volume":"22","author":[{"given":"Max","family":"Bielitza","sequence":"first","affiliation":[{"name":"European School of Chemistry","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Belorgey","sequence":"additional","affiliation":[{"name":"European School of Chemistry","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Ehrhardt","sequence":"additional","affiliation":[{"name":"European School of Chemistry","place":["France"]},{"name":"University of Heidelberg","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Johann","sequence":"additional","affiliation":[{"name":"European School of Chemistry","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don Antoine","family":"Lanfranchi","sequence":"additional","affiliation":[{"name":"European School of Chemistry","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Gallo","sequence":"additional","affiliation":[{"name":"University of Torino Medical School","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelin","family":"Schwarzer","sequence":"additional","affiliation":[{"name":"University of Torino Medical School","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Mohring","sequence":"additional","affiliation":[{"name":"Justus Liebig University of Giessen","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Jortzik","sequence":"additional","affiliation":[{"name":"Justus Liebig University of Giessen","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Williams","sequence":"additional","affiliation":[{"name":"Rush University Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Becker","sequence":"additional","affiliation":[{"name":"Justus Liebig University of Giessen","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Arese","sequence":"additional","affiliation":[{"name":"University of Torino Medical School","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mourad","family":"Elhabiri","sequence":"additional","affiliation":[{"name":"European School of Chemistry","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Davioud-Charvet","sequence":"additional","affiliation":[{"name":"European School of Chemistry","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2015,5,20]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.2174\/1385272043369548"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.11.4592-4597.2005"},{"key":"e_1_3_3_4_2","first-page":"1","article-title":"Pathophysiology of hemolysis in glucose-6-phosphate dehydrogenase deficiency","volume":"27","author":"Arese P","year":"1990","unstructured":"Arese P, and De Flora A. 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