{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:47:31Z","timestamp":1793152051851,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0006157","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T00:00:00Z","timestamp":1515628800000}}],"reference-count":73,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21 AI1257591"],"award-info":[{"award-number":["R21 AI1257591"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UL1TR000128"],"award-info":[{"award-number":["UL1TR000128"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-09-1-0429"],"award-info":[{"award-number":["W81XWH-09-1-0429"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Syrian Lebanese Associated Charities"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0006157","type":"journal-article","created":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T13:23:54Z","timestamp":1514553834000},"page":"e0006157","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["Discovery of novel, orally bioavailable, antileishmanial compounds using phenotypic screening"],"prefix":"10.1371","volume":"11","author":[{"given":"Diana","family":"Ortiz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Armand","family":"Guiguemde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared T.","family":"Hammill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela K.","family":"Carrillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhe","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Connelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Stalheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Elya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeki","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anang","family":"Shelat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Smithson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Kiplin","family":"Guy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1643-6664","authenticated-orcid":true,"given":"Scott M.","family":"Landfear","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,12,29]]},"reference":[{"issue":"9","key":"ref1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S1473-3099(07)70209-8","article-title":"Cutaneous leishmaniasis","volume":"7","author":"R Reithinger","year":"2007","journal-title":"Lancet Infect Dis"},{"issue":"6","key":"ref2","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/j.1529-8019.2009.01272.x","article-title":"Cutaneous and mucocutaneous leishmaniasis","volume":"22","author":"CV David","year":"2009","journal-title":"Dermatol Ther"},{"issue":"11","key":"ref3","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/nrmicro1748","article-title":"Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?","volume":"5","author":"F Chappuis","year":"2007","journal-title":"Nat Rev Microbiol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/S0140-6736(98)10178-2","article-title":"Leishmaniasis","volume":"354","author":"BL Herwaldt","year":"1999","journal-title":"Lancet"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-94-007-7305-9_1","article-title":"Biology of human pathogenic trypanosomatids: epidemiology, lifecycle and ultrastructure","volume":"74","author":"JC Rodrigues","year":"2014","journal-title":"Subcell Biochem"},{"issue":"10","key":"ref6","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.2174\/092986707780362862","article-title":"Chemotherapy of leishmaniasis: past, present and future","volume":"14","author":"J Mishra","year":"2007","journal-title":"Curr Med Chem"},{"issue":"12","key":"ref7","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.3390\/ijerph7124267","article-title":"Antimony toxicity","volume":"7","author":"S Sundar","year":"2010","journal-title":"Int J Environ Res Public Health"},{"issue":"Suppl 1","key":"ref8","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.trstmh.2006.03.009","article-title":"Miltefosine\u2014discovery of the antileishmanial activity of phospholipid derivatives","volume":"100","author":"SL Croft","year":"2006","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"11","key":"ref9","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1093\/jac\/dks275","article-title":"Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis","volume":"67","author":"TP Dorlo","year":"2012","journal-title":"J Antimicrob Chemother"},{"issue":"1","key":"ref10","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1128\/CMR.19.1.111-126.2006","article-title":"Drug resistance in leishmaniasis","volume":"19","author":"SL Croft","year":"2006","journal-title":"Clin Microbiol Rev"},{"issue":"11","key":"ref11","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/nrd2144","article-title":"Innovative lead discovery strategies for tropical diseases","volume":"5","author":"S Nwaka","year":"2006","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"ref12","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1017\/S003118201300142X","article-title":"Screening strategies to identify new chemical diversity for drug development to treat kinetoplastid infections","volume":"141","author":"R Don","year":"2014","journal-title":"Parasitology"},{"issue":"8","key":"ref13","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nrd4336","article-title":"The discovery of first-in-class drugs: origins and evolution","volume":"13","author":"J Eder","year":"2014","journal-title":"Nat Rev Drug Discov"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/clpt.2012.236","article-title":"Phenotypic vs. target-based drug discovery for first-in-class medicines","volume":"93","author":"DC Swinney","year":"2013","journal-title":"Clinical pharmacology and therapeutics"},{"issue":"5996","key":"ref15","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1126\/science.1193225","article-title":"Spiroindolones, a potent compound class for the treatment of malaria","volume":"329","author":"M Rottmann","year":"2010","journal-title":"Science"},{"issue":"11","key":"ref16","doi-asserted-by":"crossref","first-page":"e540","DOI":"10.1371\/journal.pntd.0000540","article-title":"Identification of potent chemotypes targeting <italic>Leishmania major<\/italic> using a high-throughput, low-stringency, computationally enhanced, small molecule screen","volume":"3","author":"ER Sharlow","year":"2009","journal-title":"PLoS Negl Trop Dis"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0169-4758(93)90181-E","article-title":"Axenic culture of <italic>Leishmania<\/italic> amastigotes","volume":"9","author":"PA Bates","year":"1993","journal-title":"Parasitol Today"},{"issue":"1","key":"ref18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0166-6851(95)00035-Y","article-title":"Isolation and characterization of the gene encoding the surface membrane 3&apos;-nucleotidase\/nuclease of <italic>Leishmania donovani<\/italic>","volume":"71","author":"A Debrabant","year":"1995","journal-title":"Mol Biochem Parasitol"},{"issue":"9","key":"ref19","doi-asserted-by":"crossref","first-page":"e0004094","DOI":"10.1371\/journal.pntd.0004094","article-title":"Development and validation of a novel <italic>Leishmania donovani<\/italic> screening cascade for high-throughput screening using a novel axenic assay with high predictivity of leishmanicidal intracellular activity","volume":"9","author":"A N\u00fchs","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"8771","DOI":"10.1038\/srep08771","article-title":"New compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites: an open resource","volume":"5","author":"I Pena","year":"2015","journal-title":"Sci Rep"},{"issue":"5","key":"ref21","doi-asserted-by":"crossref","first-page":"e675","DOI":"10.1371\/journal.pntd.0000675","article-title":"Antileishmanial high-throughput drug screening reveals drug candidates with new scaffolds","volume":"4","author":"JL Siqueira-Neto","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"issue":"4","key":"ref22","doi-asserted-by":"crossref","first-page":"e2154","DOI":"10.1371\/journal.pntd.0002154","article-title":"High content analysis of primary macrophages hosting proliferating <italic>Leishmania<\/italic> amastigotes: application to anti-leishmanial drug discovery","volume":"7","author":"N Aulner","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"issue":"7","key":"ref23","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1089\/adt.2015.652","article-title":"High-content assay for measuring intracellular growth of <italic>Leishmania<\/italic> in human macrophages","volume":"13","author":"MJ Dagley","year":"2015","journal-title":"Assay Drug Dev Technol"},{"issue":"7","key":"ref24","doi-asserted-by":"crossref","first-page":"e1253","DOI":"10.1371\/journal.pntd.0001253","article-title":"A screen against <italic>Leishmania<\/italic> intracellular amastigotes: comparison to a promastigote screen and identification of a host cell-specific hit","volume":"5","author":"G De Muylder","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"issue":"7","key":"ref25","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1128\/AAC.02398-12","article-title":"Comparison of a High-Throughput High-Content Intracellular <italic>Leishmania donovani<\/italic> Assay with an Axenic Amastigote Assay","volume":"57","author":"M De Rycker","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"issue":"6","key":"ref26","doi-asserted-by":"crossref","first-page":"e1671","DOI":"10.1371\/journal.pntd.0001671","article-title":"An image-based high-content screening assay for compounds targeting intracellular <italic>Leishmania donovani<\/italic> amastigotes in human macrophages","volume":"6","author":"JL Siqueira-Neto","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"issue":"2","key":"ref27","doi-asserted-by":"crossref","first-page":"340","DOI":"10.4269\/ajtmh.15-0448","article-title":"Antileishmanial activity of compounds derived from the Medicines for Malaria Venture Open Access Box against intracellular <italic>Leishmania majo<\/italic>r amastigotes","volume":"94","author":"M Khraiwesh","year":"2016","journal-title":"Am J Trop Med Hyg"},{"issue":"1","key":"ref28","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1177\/1087057114555846","article-title":"High-throughput screening platform for natural product-based drug discovery against 3 neglected tropical diseases: human African trypanosomiasis, leishmaniasis, and Chagas disease","volume":"20","author":"F Annang","year":"2015","journal-title":"J Biomol Screen"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s13071-016-1413-9","article-title":"Study of <italic>Leishmania<\/italic> pathogenesis in mice: experimental considerations","volume":"9","author":"C Loeuillet","year":"2016","journal-title":"Parasit Vectors"},{"issue":"Suppl 28","key":"ref30","first-page":"19.2.1","article-title":"Animal models for the analysis of immune responses to leishmaniasis","author":"DL Sacks","year":"1998","journal-title":"Current Protocols in Immunol"},{"issue":"2","key":"ref31","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/jac\/dku422","article-title":"Nitroimidazo-oxazole compound DNDI-VL-2098: an orally effective preclinical drug candidate for the treatment of visceral leishmaniasis","volume":"70","author":"S Gupta","year":"2015","journal-title":"J Antimicrob Chemother"},{"issue":"7619","key":"ref32","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/nature19339","article-title":"Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness","volume":"537","author":"S Khare","year":"2016","journal-title":"Nature"},{"issue":"7296","key":"ref33","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/nature09099","article-title":"Chemical genetics of <italic>Plasmodium falciparum<\/italic>","volume":"465","author":"WA Guiguemde","year":"2010","journal-title":"Nature"},{"issue":"7296","key":"ref34","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/nature09107","article-title":"Thousands of chemical starting points for antimalarial lead identification","volume":"465","author":"FJ Gamo","year":"2010","journal-title":"Nature"},{"issue":"8","key":"ref35","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/nchembio0807-442","article-title":"Scaffold composition and biological relevance of screening libraries","volume":"3","author":"AA Shelat","year":"2007","journal-title":"Nat Chem Biol"},{"issue":"3","key":"ref36","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.cbpa.2007.05.003","article-title":"The interdependence between screening methods and screening libraries","volume":"11","author":"AA Shelat","year":"2007","journal-title":"Curr Opin Chem Biol"},{"issue":"2","key":"ref37","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/S1359644602025722","article-title":"Nonleadlikeness and leadlikeness in biochemical screening","volume":"8","author":"GM Rishton","year":"2003","journal-title":"Drug Discov Today"},{"issue":"5","key":"ref38","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1021\/ci990423o","article-title":"Strategic pooling of compounds for high-throughput screening","volume":"39","author":"M Hann","year":"1999","journal-title":"J Chem Inf Comput Sci"},{"issue":"3","key":"ref39","first-page":"255","article-title":"Prediction of &apos;drug-likeness&apos;","volume":"54","author":"WP Walters","year":"2002","journal-title":"Adv Drug Deliv Rev"},{"issue":"15","key":"ref40","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1021\/jm9602928","article-title":"The properties of known drugs. 1. Molecular frameworks","volume":"39","author":"GW Bemis","year":"1996","journal-title":"J Med Chem"},{"issue":"4","key":"ref41","doi-asserted-by":"crossref","first-page":"633","DOI":"10.2307\/3281131","article-title":"High efficiency plating method for <italic>Leishmania<\/italic> promastigotes in semidefined or completely-defined medium","volume":"69","author":"DM Iovannisci","year":"1983","journal-title":"J Parasitol"},{"issue":"1","key":"ref42","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0166-6851(03)00142-7","article-title":"An <italic>in vitro<\/italic> system for developmental and genetic studies of <italic>Leishmania donovani<\/italic> phosphoglycans","volume":"130","author":"S Goyard","year":"2003","journal-title":"Mol Biochem Parasitol"},{"issue":"8","key":"ref43","doi-asserted-by":"crossref","first-page":"4972","DOI":"10.1128\/AAC.00850-16","article-title":"Targeting the cytochrome bc1 complex of <italic>Leishmania<\/italic> parasites for discovery of novel drugs","volume":"60","author":"D Ortiz","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"985","DOI":"10.2307\/3282883","article-title":"Continous cultivation of <italic>Trypanosoma brucei<\/italic> blood stream forms in a medium containing a low concentration of serum protein without feeder cell layers","volume":"75","author":"H Hirumi","year":"1989","journal-title":"J Parasitol"},{"issue":"4","key":"ref45","doi-asserted-by":"crossref","first-page":"e0123598","DOI":"10.1371\/journal.pone.0123598","article-title":"Identification of selective inhibitors of the <italic>Plasmodium falciparum<\/italic> hexose transporter PfHT by screening focused libraries of anti-malarial compounds","volume":"10","author":"D Ortiz","year":"2015","journal-title":"PLoS One"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.patrec.2005.10.010","article-title":"An introduction to ROC analysis","volume":"27","author":"T Fawcett","year":"2006","journal-title":"Pattern Recog Lett"},{"issue":"7","key":"ref47","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1021\/jm901137j","article-title":"New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays","volume":"53","author":"JB Baell","year":"2010","journal-title":"J Med Chem"},{"issue":"1\u20133","key":"ref48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"46","author":"CA Lipinski","year":"2001","journal-title":"Adv Drug Deliv Rev"},{"issue":"5","key":"ref49","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1021\/cc800100g","article-title":"Dual detection approach to a more accurate measure of relative purity in high-throughput characterization of compound collections","volume":"10","author":"A Lemoff","year":"2008","journal-title":"J Comb Chem"},{"issue":"3","key":"ref50","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/j.1462-5822.2004.00468.x","article-title":"Bioluminescent <italic>Leishmania<\/italic> expressing luciferase for rapid and high throughput screening of drugs acting on amastigote-harbouring macrophages and for quantitative real-time monitoring of parasitism features in living mice","volume":"7","author":"T Lang","year":"2005","journal-title":"Cell Microbiol"},{"issue":"7","key":"ref51","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1021\/np030086k","article-title":"Antiparasitic alkaloids from <italic>Psychotria klugii<\/italic>","volume":"66","author":"I Muhammad","year":"2003","journal-title":"J Nat Prod"},{"issue":"12","key":"ref52","doi-asserted-by":"crossref","first-page":"5141","DOI":"10.1021\/jm5000408","article-title":"Antileishmanial activity of a series of N(2),N(4)-disubstituted quinazoline-2,4-diamines","volume":"57","author":"KS Van Horn","year":"2014","journal-title":"J Med Chem"},{"issue":"16","key":"ref53","doi-asserted-by":"crossref","first-page":"5182","DOI":"10.1016\/j.bmc.2015.02.020","article-title":"SAR refinement of antileishmanial N(2),N(4)-disubstituted quinazoline-2,4-diamines","volume":"23","author":"X Zhu","year":"2015","journal-title":"Bioorg Med Chem"},{"issue":"5","key":"ref54","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1177\/1087057115569155","article-title":"Repurposing of the Open Access Malaria Box for Kinetoplastid Diseases Identifies Novel Active Scaffolds against Trypanosomatids","volume":"20","author":"M Kaiser","year":"2015","journal-title":"J Biomol Screen"},{"issue":"1","key":"ref55","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0166-6851(88)90147-8","article-title":"Selective inhibition of <italic>Leishmania<\/italic> dihydrofolate reductase and <italic>Leishmania<\/italic> growth by 5-benzyl-2,4-diaminopyrimidines","volume":"31","author":"W Sirawaraporn","year":"1988","journal-title":"Mol Biochem Parasitol"},{"issue":"16","key":"ref56","doi-asserted-by":"crossref","first-page":"7598","DOI":"10.1021\/acs.jmedchem.6b00698","article-title":"Profiling of Flavonol Derivatives for the Development of Antitrypanosomatidic Drugs","volume":"59","author":"C Borsari","year":"2016","journal-title":"J Med Chem"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13321-015-0069-3","article-title":"Why is Tanimoto index an appropriate choice for fingerprint-based similarity calculations?","volume":"7","author":"D Bajusz","year":"2015","journal-title":"J Cheminform"},{"issue":"7","key":"ref58","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1021\/jm301687p","article-title":"Optimization of chloronitrobenzamides (CNBs) as therapeutic leads for human African trypanosomiasis (HAT)","volume":"56","author":"JY Hwang","year":"2013","journal-title":"J Med Chem"},{"issue":"3","key":"ref59","doi-asserted-by":"crossref","first-page":"485","DOI":"10.2217\/nnm.10.10","article-title":"Nanomicellar formulations for sustained drug delivery: strategies and underlying principles","volume":"5","author":"R Trivedi","year":"2010","journal-title":"Nanomedicine (Lond)"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1111\/j.1476-5381.2010.01127.x","article-title":"Principles of early drug discovery","volume":"162","author":"JP Hughes","year":"2011","journal-title":"British J Pharm"},{"issue":"4","key":"ref61","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1039\/C4OB02137A","article-title":"Synthesis and tautomerization of hydroxylated isoflavones bearing heterocyclic hemi-aminals","volume":"13","author":"MS Frasinyuk","year":"2015","journal-title":"Org Biomol Chem"},{"issue":"8","key":"ref62","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/nrd.2017.111","article-title":"Opportunities and challenges in phenotypic drug discovery: an industry perspective","volume":"16","author":"JG Moffat","year":"2017","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"ref63","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.molbiopara.2008.07.005","article-title":"An expression system to screen for inhibitors of parasite glucose transporters","volume":"162","author":"T Feistel","year":"2008","journal-title":"Mol Biochem Parasitol"},{"issue":"1","key":"ref64","doi-asserted-by":"crossref","first-page":"e51864","DOI":"10.1371\/journal.pone.0051864","article-title":"Triphenylmethane derivatives have high in vitro and in vivo activity against the main causative agents of cutaneous leishmaniasis","volume":"8","author":"RC de Souza Pietra","year":"2013","journal-title":"PLoS One"},{"issue":"10","key":"ref65","doi-asserted-by":"crossref","first-page":"6463","DOI":"10.1128\/AAC.05131-14","article-title":"Antileishmanial activity of Disulfiram and Thiuram disulfide analogs in an <italic>ex vivo<\/italic> model system Is selectively enhanced by the addition of divalent metal ions","volume":"59","author":"AG Peniche","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"issue":"9","key":"ref66","doi-asserted-by":"crossref","first-page":"5026","DOI":"10.1128\/IAI.70.9.5026-5035.2002","article-title":"Activation of p38 mitogen-activated protein kinase attenuates Leishmania donovani infection in macrophages","volume":"70","author":"M Junghae","year":"2002","journal-title":"Infect Immun"},{"issue":"11","key":"ref67","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1128\/AAC.33.11.1860","article-title":"Antileishmanial activities of 2,4-diaminoquinazoline putative dihydrofolate reductase inhibitors","volume":"33","author":"JD Berman","year":"1989","journal-title":"Antimicrob Agents Chemother"},{"issue":"21","key":"ref68","doi-asserted-by":"crossref","first-page":"13883","DOI":"10.1074\/jbc.272.21.13883","article-title":"The roles of pteridine reductase 1 and dihydrofolate reductase-thymidylate synthase in pteridine metabolism in the protozoan parasite <italic>Leishmania majo<\/italic>r","volume":"272","author":"B Nare","year":"1997","journal-title":"J Biol Chem"},{"issue":"3","key":"ref69","doi-asserted-by":"crossref","DOI":"10.3390\/molecules22030426","article-title":"Chroman-4-One Derivatives Targeting Pteridine Reductase 1 and Showing Anti-Parasitic Activity","volume":"22","author":"F Di Pisa","year":"2017","journal-title":"Molecules"},{"issue":"3","key":"ref70","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1111\/j.1365-2958.2010.07236.x","article-title":"<italic>Trypanosoma brucei<\/italic> pteridine reductase 1 is essential for survival in vitro and for virulence in mice","volume":"77","author":"N Sienkiewicz","year":"2010","journal-title":"Mol Microbiol"},{"issue":"5","key":"ref71","doi-asserted-by":"crossref","first-page":"697","DOI":"10.3892\/br.2013.129","article-title":"Soy isoflavone: The multipurpose phytochemical (Review)","volume":"1","author":"Q Wang","year":"2013","journal-title":"Biomed Rep"},{"issue":"4304","key":"ref72","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/169706a0","article-title":"A new synthesis of isoflavones","volume":"169","author":"W Baker","year":"1952","journal-title":"Nature"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/jhet.5570410401","article-title":"Synthesis of isoflavones","volume":"41","author":"A L\u00e9vai","year":"2004","journal-title":"J Hetrocyclic Chem"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0006157","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T00:00:00Z","timestamp":1515628800000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0006157","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T11:40:38Z","timestamp":1540208438000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0006157"}},"subtitle":[],"editor":[{"given":"Igor C.","family":"Almeida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,12,29]]},"references-count":73,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2017,12,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0006157","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0006157","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,29]]}}}