{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:13:24Z","timestamp":1792588404238,"version":"4.5.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2013,12,20]],"date-time":"2013-12-20T00:00:00Z","timestamp":1387497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0082504","type":"journal-article","created":{"date-parts":[[2013,12,20]],"date-time":"2013-12-20T22:07:37Z","timestamp":1387577257000},"page":"e82504","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":31,"title":["Synthetic 1,4-Pyran Naphthoquinones Are Potent Inhibitors of Dengue Virus Replication"],"prefix":"10.1371","volume":"8","author":[{"given":"Emmerson C. B.","family":"da Costa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Amorim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando C.","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle P.","family":"Papa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana B.","family":"de Arruda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronaldo","family":"Mohana-Borges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor F.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amilcar","family":"Tanuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana J.","family":"da Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina B.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,12,20]]},"reference":[{"key":"ref1","article-title":"Scientific Working Group Report on Dengue. Switzerland","year":"2006"},{"key":"ref2","article-title":"Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. Switzerland","year":"2009"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1038\/nrmicro2460","article-title":"Dengue: a continuing global threat","volume":"8","author":"MG Guzman","year":"2010","journal-title":"Nat Rev Microbiol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.vaccine.2004.03.069","article-title":"Dengue virus: molecular basis of cell entry and pathogenesis, 25-27 June 2003, Vienna, Austria","volume":"23","author":"SB Halstead","year":"2005","journal-title":"Vaccine"},{"key":"ref5","first-page":"e1648","article-title":"Surveillance of dengue fever virus: a review of epidemiological models and early warning systems","volume":"6","author":"V Racloz","year":"2012"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1016\/S0140-6736(12)61428-7","article-title":"Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial","volume":"380","author":"A Sabchareon","year":"2012","journal-title":"Lancet"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.antiviral.2008.08.004","article-title":"Molecular targets for flavivirus drug discovery","volume":"81","author":"A Sampath","year":"2009","journal-title":"Antiviral Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1006\/viro.1998.9213","article-title":"Recombinant dengue virus type 1 NS3 protein exhibits specific viral RNA binding and NTPase activity regulated by the NS5 protein","volume":"246","author":"T Cui","year":"1998","journal-title":"Virology"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1006\/viro.1993.1587","article-title":"The NS 3 nonstructural protein of flaviviruses contains an RNA triphosphatase activity","volume":"197","author":"G Wengler","year":"1993","journal-title":"Virology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"7232","DOI":"10.1128\/JVI.69.11.7232-7243.1995","article-title":"Evidence that flavivirus NS1-NS2A cleavage is mediated by a membrane-bound host protease in the endoplasmic reticulum","volume":"69","author":"B Falgout","year":"1995","journal-title":"J Virol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"45762","DOI":"10.1074\/jbc.M107360200","article-title":"Activity of recombinant dengue 2 virus NS3 protease in the presence of a truncated NS2B co-factor, small peptide substrates, and inhibitors","volume":"276","author":"D Leung","year":"2001","journal-title":"J Biol Chem"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"23311","DOI":"10.1074\/jbc.M301283200","article-title":"ATP binding modulates the nucleic acid affinity of hepatitis C virus helicase","volume":"278","author":"MK Levin","year":"2003","journal-title":"J Biol Chem"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nrd1853","article-title":"Viral and cellular RNA helicases as antiviral targets","volume":"4","author":"AD Kwong","year":"2005","journal-title":"Nat Rev Drug Discov"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1128\/JVI.01788-07","article-title":"Crystal structure of the NS3 protease-helicase from dengue virus","volume":"82","author":"D Luo","year":"2008","journal-title":"J Virol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"10278","DOI":"10.1128\/JVI.79.16.10278-10288.2005","article-title":"Structure of the Dengue virus helicase\/nucleoside triphosphatase catalytic domain at a resolution of 2.4 A","volume":"79","author":"T Xu","year":"2005","journal-title":"J Virol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1016\/j.ejmech.2011.03.012","article-title":"Synthesis and anti-Trypanosoma cruzi activity of \u03b2-lapachone analogues","volume":"46","author":"SB Ferreira","year":"2011","journal-title":"Eur J Med Chem"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.1016\/j.bmc.2006.04.046","article-title":"Trypanocidal agents with low cytotoxicity to mammalian cell line: a comparison of the theoretical and biological features of lapachone derivatives","volume":"14","author":"VF Ferreira","year":"2006","journal-title":"Bioorg Med Chem"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s00436-006-0153-8","article-title":"Oxyrane derivative of alpha-lapachone is potent growth inhibitor of Trypanosoma cruzi epimastigote forms","volume":"99","author":"A Jorqueira","year":"2006","journal-title":"Parasitol Res"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"4793","DOI":"10.1039\/c0ob00277a","article-title":"Strategies for the synthesis of bioactive pyran naphthoquinones","volume":"8","author":"VF Ferreira","year":"2010","journal-title":"Org Biomol Chem"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"5387","DOI":"10.1016\/j.bmcl.2008.09.053","article-title":"Semisynthesis and antitumoral activity of 2-acetylfuranonaphthoquinone and other naphthoquinone derivatives from lapachol","volume":"18","author":"KO Eyong","year":"2008","journal-title":"Bioorg Med Chem Lett"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/cbdv.200590009","article-title":"Antiplasmodial activity of naphthoquinones related to lapachol and beta-lapachone","volume":"2","author":"E P\u00e9rez-Sacau","year":"2005","journal-title":"Chem Biodivers"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1021\/jm900865m","article-title":"3-arylamino and 3-alkoxy-nor-beta-lapachone derivatives: synthesis and cytotoxicity against cancer cell lines","volume":"53","author":"EN Da Silva","year":"2010","journal-title":"J Med Chem"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"4315","DOI":"10.1039\/c1ob05209h","article-title":"Synthesis of new 9-hydroxy-\u03b1- and 7-hydroxy-\u03b2-pyran naphthoquinones and cytotoxicity against cancer cell lines","volume":"9","author":"DR Da Rocha","year":"2011","journal-title":"Org Biomol Chem"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1590\/S0103-50532010000700017","article-title":"Theoretical Studies of the Tautomerism in 3-(2-R-Phenylhydrazono)-naphthalene-1,2,4-triones: Synthesis of Copper(II) Complexes and Studies of Antibacterial and Antitumor Activities","volume":"21","author":"AI Francisco","year":"2010","journal-title":"Journal of the Brazilian Chemical Society"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1128\/IAI.73.2.1191-1195.2005","article-title":"Distinct Leishmania braziliensis isolates induce different paces of chemokine expression patterns","volume":"73","author":"MJ Teixeira","year":"2005","journal-title":"Infect Immun"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1590\/S0074-02762004000700017","article-title":"Antileishmanial activity of lapachol analogues","volume":"99","author":"NM Lima","year":"2004","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1590\/S0103-50532009000100026","article-title":"Antitumoral, antileishmanial and antimalarial activity of pentacyclic 1,4-naphthoquinone derivatives","volume":"20","author":"CD Netto","year":"2009","journal-title":"Journal of the Brazilian Chemical Society"},{"key":"ref28","first-page":"822","article-title":"Molluscicidal hydroxynaphthoquinones and derivatives: correlation between their redox potentials and activity against Biomphalaria glabrata","volume":"13","author":"NMF Lima","year":"2002","journal-title":"Journal of the Brazilian Chemical Society"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.bmc.2004.09.043","article-title":"Molluscicidal activity of synthetic lapachol amino and hydrogenated derivatives","volume":"13","author":"TMS Silva","year":"2005","journal-title":"Bioorg Med Chem"},{"key":"ref30","first-page":"2007","article-title":"Lapachol : an overview","author":"H Hussain","year":"2007","journal-title":"Arkivok"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1055\/s-2006-959504","article-title":"Comparison of antibacterial and antifungal activities of lapachol and beta-lapachone","volume":"60","author":"P Guiraud","year":"1994","journal-title":"Planta Med"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1080\/00034983.1978.11719356","article-title":"In vitro and in vivo evaluation of the toxicity of 1,4-naphthoquinone and 1,2-naphthoquinone derivatives against Trypanosoma cruzi","volume":"72","author":"JN Lopes","year":"1978","journal-title":"Ann Trop Med Parasitol"},{"key":"ref33","first-page":"3","article-title":"Quinone structure-antitumor activity relationships","volume":"4","author":"JS Driscoll","year":"1974","journal-title":"Cancer Chemother Rep 2"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.2174\/1389557043402900","article-title":"Synthetic approaches to the 2003 new drugs","volume":"4","author":"KK-C Liu","year":"2004","journal-title":"Mini Rev Med Chem"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1016\/S0960-894X(99)00489-8","article-title":"2-chloro-3-substituted-1,4-naphthoquinone inactivators of human cytomegalovirus protease","volume":"9","author":"P Ertl","year":"1999","journal-title":"Bioorg Med Chem Lett"},{"key":"ref36","first-page":"605","article-title":"Inhibition of potentially lethal DNA damage repair in human tumor cells by beta-lapachone, an activator of topoisomerase I","volume":"49","author":"DA Boothman","year":"1989","journal-title":"Cancer Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0027-5107(94)90048-5","article-title":"International Commission for Protection Against Environmental Mutagens and Carcinogens. Mutagenicity and carcinogenicity of topoisomerase-interactive agents","volume":"309","author":"RD Anderson","year":"1994","journal-title":"Mutat Res"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"425","DOI":"10.2174\/1389200023337388","article-title":"The metabolism and toxicity of quinones, quinonimines, quinone methides, and quinone-thioethers","volume":"3","author":"TJ Monks","year":"2002","journal-title":"Curr Drug Metab"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1590\/S0103-50532009000800014","article-title":"Synthesis of \u03b1- and \u03b2-Lapachone Derivatives from Hetero Diels-Alder Trapping of Alkyl and Aryl","volume":"20","author":"FC Da Silva","year":"2009","journal-title":"Journal of the Brazilian Chemical Society"},{"key":"ref40","article-title":"Synthesis and comparative SAR\/SSR study of a series of \u03b1 and \u03b2-lapachone analogues with anti-cancer cytotoxicity and DNA topoisomerase inhibitory activity","volume":"0","author":"S Ferreira","year":"2013","journal-title":"Medchemcomm submited"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1126\/science.65.1686.401","article-title":"The nature of the &quot;inorganic phosphate&quot; in voluntary muscle","volume":"65","author":"CH Fiske","year":"1927","journal-title":"Science"},{"key":"ref42","first-page":"493","article-title":"A simple method of estimating 50 per cent end-points","volume":"27","author":"L Reed","year":"1938","journal-title":"American Journal of Hygiene"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"4977","DOI":"10.1128\/JCM.43.10.4977-4983.2005","article-title":"Serotype-specific detection of dengue viruses in a fourplex real-time reverse transcriptase PCR assay","volume":"43","author":"BW Johnson","year":"2005","journal-title":"J Clin Microbiol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.virol.2004.07.004","article-title":"The RNA helicase, nucleotide 5\u2019-triphosphatase, and RNA 5&apos;-triphosphatase activities of Dengue virus protein NS3 are Mg2+-dependent and require a functional Walker B motif in the helicase catalytic core","volume":"328","author":"D Benarroch","year":"2004","journal-title":"Virology"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.febslet.2004.04.072","article-title":"Direct fluorometric measurement of hepatitis C virus helicase activity","volume":"567","author":"AM Boguszewska-Chachulska","year":"2004","journal-title":"FEBS Lett"},{"key":"ref46","first-page":"e36244","article-title":"Novel ATP-independent RNA annealing activity of the dengue virus NS3 helicase","volume":"7","author":"LG Gebhard","year":"2012"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"3108","DOI":"10.1128\/JVI.73.4.3108-3116.1999","article-title":"The serine protease and RNA-stimulated nucleoside triphosphatase and RNA helicase functional domains of dengue virus type 2 NS3 converge within a region of 20 amino acids","volume":"73","author":"H Li","year":"1999","journal-title":"J Virol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"13708","DOI":"10.1128\/JVI.78.24.13708-13716.2004","article-title":"Identification of residues in the dengue virus type 2 NS2B cofactor that are critical for NS3 protease activation","volume":"78","author":"P Niyomrattanakit","year":"2004","journal-title":"J Virol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1093\/jac\/dks147","article-title":"Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug","volume":"67","author":"E Mastrangelo","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"ref50","first-page":"e37244","article-title":"An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro","volume":"7","author":"T De Burghgraeve","year":"2012"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0082504","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T18:20:04Z","timestamp":1597256404000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0082504"}},"subtitle":[],"editor":[{"given":"Robert\u00a0J.","family":"Geraghty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,12,20]]},"references-count":50,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2013,12,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0082504","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,20]]}}}