{"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":1791311563707,"version":"4.3.1"},"reference-count":58,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Methylene blue and a series of recently developed 1,4-naphthoquinones, including 3-[4-(substituted)benzyl]-menadiones, are potent antimalarial agents\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            . The activity of these structurally diverse compounds against the human malaria parasite\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>\n            might involve their peculiar redox properties. According to the current theory, redox-active methylene blue and 3-[4-(trifluoromethyl)benzyl]-menadione are \u201csubversive substrates.\u201d These agents are thought to shuttle electrons from reduced flavoproteins to acceptors such as hemoglobin-associated or free Fe(III)-protoporphyrin IX. The reduction of Fe(III)-protoporphyrin IX could subsequently prevent essential hemoglobin digestion and heme detoxification in the parasite. Alternatively, owing to their structures and redox properties, methylene blue and 1,4-naphthoquinones might also affect the mitochondrial electron transport chain. Here, we tested the latter hypothesis using an established system of transgenic\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n            cell lines and the antimalarial agents atovaquone and chloroquine as controls. In contrast to atovaquone, methylene blue and 3-[4-(trifluoromethyl)benzyl]-menadione do not inhibit the mitochondrial electron transport chain. A systematic comparison of the morphologies of drug-treated parasites furthermore suggests that the three drugs do not share a mechanism of action. Our findings support the idea that methylene blue and 3-[4-(trifluoromethyl)benzyl]-menadione exert their antimalarial activity as redox-active subversive substrates.\n          <\/jats:p>","DOI":"10.1128\/aac.02248-12","type":"journal-article","created":{"date-parts":[[2013,2,26]],"date-time":"2013-02-26T04:56:06Z","timestamp":1361854566000},"page":"2114-2120","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["The Antimalarial Activities of Methylene Blue and the 1,4-Naphthoquinone 3-[4-(Trifluoromethyl)Benzyl]-Menadione Are Not Due to Inhibition of the Mitochondrial Electron Transport Chain"],"prefix":"10.1128","volume":"57","author":[{"given":"Katharina","family":"Ehrhardt","sequence":"first","affiliation":[{"name":"Department of Parasitology, Ruprecht-Karls University, Heidelberg, Germany"},{"name":"European School of Chemistry, Polymers, and Materials, University of Strasbourg and Centre National de la Recherche Scientifique, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Davioud-Charvet","sequence":"additional","affiliation":[{"name":"European School of Chemistry, Polymers, and Materials, University of Strasbourg and Centre National de la Recherche Scientifique, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangjun","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhil B.","family":"Vaidya","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lanzer","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Ruprecht-Karls University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Deponte","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Ruprecht-Karls University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(92)90213-3"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.7.3961"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01515.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.091208.073424"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205651109"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.21.11865"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/35005132"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.04.042"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500388200"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2007.02.014"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00937-10"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.290973"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2011-0255"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05572"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2012.09.007"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(94)00158-T"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.162081"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.05049-11"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001630"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005318"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3156.2010.02526.x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja201729z"},{"key":"e_1_3_2_24_2","first-page":"375","volume-title":"Drug discovery in infectious diseases","author":"Davioud-Charvet E","year":"2011","unstructured":"Davioud-CharvetE LanfranchiDA. 2011. 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