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The Global Health Primer. 2015. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.bvgh.org\/Current-Programs\/Neglected-Disease-Product-Pipelines\/Global-Health-Primer.aspx\" xlink:type=\"simple\">http:\/\/www.bvgh.org\/Current-Programs\/Neglected-Disease-Product-Pipelines\/Global-Health-Primer.aspx<\/ext-link>."},{"key":"ref15","unstructured":"Anon. Oxachagas. 2014. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.dndi.org\/diseases-projects\/portfolio\/oxachagas.html\" xlink:type=\"simple\">http:\/\/www.dndi.org\/diseases-projects\/portfolio\/oxachagas.html<\/ext-link>."},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1093\/jac\/dks027","article-title":"Safety of benznidazole use in the treatment of chronic Chagas&apos; disease","volume":"67","author":"AM Hasslocher-Moreno","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1586\/14787210.7.2.157","article-title":"Side effects of benznidazole as treatment in chronic Chagas disease: fears and realities","volume":"7","author":"R Viotti","year":"2009","journal-title":"Expert Rev Anti Infect Ther"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1021\/jm400012e","article-title":"Antitrypanosomal lead discovery: identification of a ligand-efficient inhibitor of Trypanosoma cruzi CYP51 and parasite growth","volume":"56","author":"G Andriani","year":"2013","journal-title":"J Med Chem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"31602","DOI":"10.1074\/jbc.M113.497990","article-title":"Complexes of Trypanosoma cruzi sterol 14alpha-demethylase (CYP51) with two pyridine-based drug candidates for Chagas disease: structural basis for pathogen selectivity","volume":"288","author":"TY Hargrove","year":"2013","journal-title":"J Biol Chem"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1093\/infdis\/jit042","article-title":"VNI cures acute and chronic experimental Chagas disease","volume":"208","author":"F Villalta","year":"2013","journal-title":"J Infect Dis"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1021\/ml500010m","article-title":"R-Configuration of 4-Aminopyridyl-Based Inhibitors of CYP51 Confers Superior Efficacy Against Trypanosoma cruzi","volume":"5","author":"JY Choi","year":"2014","journal-title":"ACS Med Chem Lett"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.1128\/AAC.00070-13","article-title":"In vitro and in vivo studies of the antiparasitic activity of sterol 14alpha-demethylase (CYP51) inhibitor VNI against drug-resistant strains of Trypanosoma cruzi","volume":"57","author":"N Soeiro Mde","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"e1736","DOI":"10.1371\/journal.pntd.0001736","article-title":"Diverse inhibitor chemotypes targeting Trypanosoma cruzi CYP51","volume":"6","author":"SS Gunatilleke","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"ref24","first-page":"966","article-title":"Posaconazole versus benznidazole for chronic Chagas&apos; disease","volume":"371","author":"I Molina","year":"2014","journal-title":"N Engl J Med"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"e1870","DOI":"10.1371\/journal.pntd.0001870","article-title":"Fexinidazole: a potential new drug candidate for Chagas disease","volume":"6","author":"MT Bahia","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"ref26","unstructured":"Anon. Fexinidazole (Chagas). 2014. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.dndi.org\/diseases-projects\/portfolio\/fexinidazole-chagas.html\" xlink:type=\"simple\">http:\/\/www.dndi.org\/diseases-projects\/portfolio\/fexinidazole-chagas.html<\/ext-link>."},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e2370","DOI":"10.1371\/journal.pntd.0002370","article-title":"Non-peptidic cruzain inhibitors with trypanocidal activity discovered by virtual screening and in vitro assay","volume":"7","author":"HJ Wiggers","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1128\/AAC.01855-13","article-title":"Reversible cysteine protease inhibitors show promise for a Chagas disease cure","volume":"58","author":"M Ndao","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3762\/bjoc.9.3","article-title":"Chemical-biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target","volume":"9","author":"JW Choy","year":"2013","journal-title":"Beilstein J Org Chem"},{"key":"ref30","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"},{"key":"ref31","article-title":"Probe Reports from the NIH Molecular Libraries Program","author":"LC Carmody","year":"2010"},{"key":"ref32","article-title":"Probe Reports from the NIH Molecular Libraries Program","author":"LC Carmody","year":"2010"},{"key":"ref33","article-title":"Probe Reports from the NIH Molecular Libraries Program","author":"LC Carmody","year":"2010"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"7197","DOI":"10.1016\/j.bmcl.2011.09.057","article-title":"Identification of small-molecule inhibitors of Trypansoma cruzi replication","volume":"21","author":"AR Germain","year":"2011","journal-title":"Bioorg Med Chem Lett"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1177\/1087057114553103","article-title":"Lead identification to clinical candidate selection: drugs for Chagas disease","volume":"20","author":"RJ Neitz","year":"2015","journal-title":"J Biomol Screen"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"e0003493","DOI":"10.1371\/journal.pntd.0003493","article-title":"Automated high-content assay for compounds selectively toxic to Trypanosoma cruzi in a myoblastic cell line","volume":"9","author":"J Alonso-Padilla","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"e3259","DOI":"10.1371\/journal.pntd.0003259","article-title":"High throughput screening for anti-Trypanosoma cruzi drug discovery","volume":"8","author":"J Alonso-Padilla","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"e1298","DOI":"10.1371\/journal.pntd.0001298","article-title":"Activity in vivo of anti-Trypanosoma cruzi compounds selected from a high throughput screening","volume":"5","author":"G Andriani","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"e2977","DOI":"10.1371\/journal.pntd.0002977","article-title":"Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi","volume":"8","author":"JD Planer","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1128\/AAC.01777-09","article-title":"Image-based high-throughput drug screening targeting the intracellular stage of Trypanosoma cruzi, the agent of Chagas&apos; disease","volume":"54","author":"JC Engel","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1177\/1087057114550585","article-title":"Chagas disease drug discovery: toward a new era","volume":"20","author":"E Chatelain","year":"2015","journal-title":"J Biomol Screen"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1007\/s11095-012-0741-5","article-title":"Combining cheminformatics methods and pathway analysis to identify molecules with whole-cell activity against Mycobacterium tuberculosis","volume":"29","author":"M Sarker","year":"2012","journal-title":"Pharm Res"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1039\/b917766c","article-title":"A collaborative database and computational models for tuberculosis drug discovery","volume":"6","author":"S Ekins","year":"2010","journal-title":"Mol Biosyst"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"e00301","DOI":"10.1128\/mBio.00301-10","article-title":"Essential metabolites of Mycobacterium tuberculosis and their mimics","volume":"2","author":"G Lamichhane","year":"2011","journal-title":"MBio"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1021\/mp900163d","article-title":"Computational models for drug inhibition of the human apical sodium-dependent bile acid transporter","volume":"6","author":"X Zheng","year":"2009","journal-title":"Mol Pharm"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1039\/c0mb00104j","article-title":"Analysis and hit filtering of a very large library of compounds screened against Mycobacterium tuberculosis","volume":"6","author":"S Ekins","year":"2010","journal-title":"Mol Biosyst"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1007\/s11095-011-0413-x","article-title":"Validating new tuberculosis computational models with public whole cell screening aerobic activity datasets","volume":"28","author":"S Ekins","year":"2011","journal-title":"Pharm Res"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ejps.2009.10.007","article-title":"Computational discovery of novel trypanosomicidal drug-like chemicals by using bond-based non-stochastic and stochastic quadratic maps and linear discriminant analysis","volume":"39","author":"JA Castillo-Garit","year":"2010","journal-title":"Eur J Pharm Sci"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1016\/j.bmcl.2005.12.087","article-title":"New ligand-based approach for the discovery of antitrypanosomal compounds","volume":"16","author":"MC Vega","year":"2006","journal-title":"Bioorg Med Chem Lett"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"6264","DOI":"10.1016\/j.bmc.2005.06.049","article-title":"A novel non-stochastic quadratic fingerprints-based approach for the &apos;in silico&apos; discovery of new antitrypanosomal compounds","volume":"13","author":"A Montero-Torres","year":"2005","journal-title":"Bioorg Med Chem"},{"key":"ref51","unstructured":"Anon. Trypanosoma cruzi KEGG Genes Database. 2015. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.genome.jp\/dbget-bin\/www_bfind?T01012\" xlink:type=\"simple\">http:\/\/www.genome.jp\/dbget-bin\/www_bfind?T01012<\/ext-link>."},{"key":"ref52","unstructured":"Doyle M, McRae JI, Saunders EC, McConville MJ, Likic VA. Summary of Leishmania major, Strain strain Friedlin, version 18.5 2015. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/biocyc.org\/LEISH\/organism-summary?object=LEISH\" xlink:type=\"simple\">http:\/\/biocyc.org\/LEISH\/organism-summary?object=LEISH<\/ext-link>."},{"key":"ref53","unstructured":"Shameer S. Summary of Trypanosoma brucei, version 18.5 <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/biocyc.org\/TRYPANO\/organism-summary?object=TRYPANO\" xlink:type=\"simple\">http:\/\/biocyc.org\/TRYPANO\/organism-summary?object=TRYPANO<\/ext-link>."},{"key":"ref54","doi-asserted-by":"crossref","first-page":"e384","DOI":"10.1371\/journal.pntd.0000384","article-title":"Identification of three classes of heteroaromatic compounds with activity against intracellular Trypanosoma cruzi by chemical library screening","volume":"3","author":"E Bettiol","year":"2009","journal-title":"PLoS Negl Trop Dis"},{"key":"ref55","unstructured":"Anon. Open innovation portal. 2015. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.dndi.org\/diseases-projects\/open-innovation.html\" xlink:type=\"simple\">http:\/\/www.dndi.org\/diseases-projects\/open-innovation.html<\/ext-link>"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.tube.2013.12.001","article-title":"Bayesian models for screening and TB Mobile for target inference with Mycobacterium tuberculosis","volume":"94","author":"S Ekins","year":"2014","journal-title":"Tuberculosis (Edinb)"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1007\/s11095-013-1172-7","article-title":"Combining computational methods for hit to lead optimization in Mycobacterium tuberculosis drug discovery","volume":"31","author":"S Ekins","year":"2014","journal-title":"Pharm Res"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1021\/ci400480s","article-title":"Fusing dual-event data sets for Mycobacterium tuberculosis machine learning models and their evaluation","volume":"53","author":"S Ekins","year":"2013","journal-title":"J Chem Inf Model"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1021\/ci500264r","article-title":"Are bigger data sets better for machine learning? Fusing single-point and dual-event dose response data for Mycobacterium tuberculosis","volume":"54","author":"S Ekins","year":"2014","journal-title":"J Chem Inf Model"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1021\/ci500077v","article-title":"Looking back to the future: predicting in vivo efficacy of small molecules versus Mycobacterium tuberculosis","volume":"54","author":"S Ekins","year":"2014","journal-title":"J Chem Inf Model"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"e63240","DOI":"10.1371\/journal.pone.0063240","article-title":"Enhancing hit identification in Mycobacterium tuberculosis drug discovery using validated dual-event Bayesian models","volume":"8","author":"S Ekins","year":"2013","journal-title":"PLoS One"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13321-014-0038-2","article-title":"New target prediction and visualization tools incorporating open source molecular fingerprints for TB Mobile 2.0","volume":"6","author":"AM Clark","year":"2014","journal-title":"J Cheminform"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1758-2946-5-13","article-title":"TB Mobile: a mobile app for anti-tuberculosis molecules with known targets","volume":"5","author":"S Ekins","year":"2013","journal-title":"J Cheminform"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1039\/b917766c","article-title":"A Collaborative Database And Computational Models For Tuberculosis Drug Discovery","volume":"6","author":"S Ekins","year":"2010","journal-title":"Mol BioSystems"},{"key":"ref65","unstructured":"Anon. Collaborative Drug Discovery, Inc. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.collaborativedrug.com\/register\" xlink:type=\"simple\">http:\/\/www.collaborativedrug.com\/register<\/ext-link>."},{"key":"ref66","unstructured":"Anon. CDD Public. 2015. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.collaborativedrug.com\/pages\/public_access\" xlink:type=\"simple\">https:\/\/www.collaborativedrug.com\/pages\/public_access<\/ext-link>."},{"key":"ref67","doi-asserted-by":"crossref","first-page":"D459","DOI":"10.1093\/nar\/gkt1103","article-title":"The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway\/Genome Databases","volume":"42","author":"R Caspi","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"D742","DOI":"10.1093\/nar\/gkr1014","article-title":"The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway\/genome databases","volume":"40","author":"R Caspi","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref69","doi-asserted-by":"crossref","DOI":"10.1128\/genomeA.01114-13","article-title":"Trypanosoma cruzi Clone Dm28c Draft Genome Sequence","volume":"2","author":"EC Grisard","year":"2014","journal-title":"Genome Announc"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.1093\/nar\/gkl334","article-title":"The pathway tools cellular overview diagram and omics viewer","volume":"34","author":"S Paley","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"424","DOI":"10.4056\/sigs.1794338","article-title":"The pathway tools pathway prediction algorithm","volume":"5","author":"PD Karp","year":"2011","journal-title":"Stand Genomic Sci"},{"key":"ref72","first-page":"162","article-title":"Bayesian Models for Screening and TB Mobile for Target Inference with Mycobacterium tuberculosis Tuberculosis (Edinb)","volume":"94","author":"S Ekins","year":"2014","journal-title":"Bayesian Models for Screening and TB Mobile for Target Inference with Mycobacterium tuberculosis Tuberculosis (Edinb)"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"e63240","DOI":"10.1371\/journal.pone.0063240","article-title":"Enhancing Hit Identification in Mycobacterium tuberculosis Drug Discovery Using Validated Dual-Event Bayesian Models","volume":"8","author":"S Ekins","year":"2013","journal-title":"PLOSONE"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.chembiol.2013.01.011","article-title":"Bayesian models leveraging bioactivity and cytotoxicity information for drug discovery","volume":"20","author":"S Ekins","year":"2013","journal-title":"Chem Biol"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1021\/ci800143n","article-title":"Global Bayesian models for the prioritization of antitubercular agents","volume":"48","author":"P Prathipati","year":"2008","journal-title":"J Chem Inf Model"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1002\/cmdc.200700026","article-title":"Analysis of Pharmacology Data and the Prediction of Adverse Drug Reactions and Off-Target Effects from Chemical Structure","volume":"2","author":"A Bender","year":"2007","journal-title":"ChemMedChem"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1021\/ci0601315","article-title":"Improved naive Bayesian modeling of numerical data for absorption, distribution, metabolism and excretion (ADME) property prediction","volume":"46","author":"AE Klon","year":"2006","journal-title":"J Chem Inf Model"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s11030-006-9041-5","article-title":"Cheminformatics analysis and learning in a data pipelining environment","volume":"10","author":"M Hassan","year":"2006","journal-title":"Mol Divers"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1177\/1087057105281365","article-title":"Using extended-connectivity fingerprints with Laplacian-modified Bayesian analysis in high-throughput screening follow-up","volume":"10","author":"D Rogers","year":"2005","journal-title":"J Biomol Screen"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1124\/dmd.106.014613","article-title":"Computational approaches that predict metabolic intermediate complex formation with CYP3A4 (+b5)","volume":"35","author":"DR Jones","year":"2007","journal-title":"Drug Metab Dispos"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"340","DOI":"10.2174\/1568026613666131127160819","article-title":"Seeding collaborations to advance kinase science with the GSK Published Kinase Inhibitor Set (PKIS)","volume":"14","author":"DH Drewry","year":"2014","journal-title":"Curr Top Med Chem"},{"key":"ref82","unstructured":"Gagaring K, Borboa R, Francek C, Chen Z, Buenviaje J, Plouffe D, et al. Novartis-GNF Malaria Box. ChEMBL-NTD (<ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.ebi.ac.uk\/chemblntd\" xlink:type=\"simple\">www.ebi.ac.uk\/chemblntd<\/ext-link>)"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"6989","DOI":"10.1021\/jm500448u","article-title":"4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency","volume":"57","author":"CM Calvet","year":"2014","journal-title":"J Med Chem"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"3584","DOI":"10.1128\/AAC.01451-09","article-title":"Hydroxymethylnitrofurazone is active in a murine model of Chagas&apos; disease","volume":"54","author":"C Davies","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00726-007-0537-9","article-title":"Targeting the polyamine biosynthetic enzymes: a promising approach to therapy of African sleeping sickness, Chagas&apos; disease, and leishmaniasis","volume":"33","author":"O Heby","year":"2007","journal-title":"Amino Acids"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/(SICI)1097-0134(199601)24:1<73::AID-PROT5>3.0.CO;2-P","article-title":"Crystal structure of the Trypanosoma cruzi trypanothione reductase.mepacrine complex","volume":"24","author":"EM Jacoby","year":"1996","journal-title":"Proteins"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"29493","DOI":"10.1074\/jbc.M403187200","article-title":"Two interacting binding sites for quinacrine derivatives in the active site of trypanothione reductase: a template for drug design","volume":"279","author":"A Saravanamuthu","year":"2004","journal-title":"J Biol Chem"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"e58010","DOI":"10.1371\/journal.pone.0058010","article-title":"Application of a novel microtitre plate-based assay for the discovery of new inhibitors of DNA gyrase and DNA topoisomerase VI","volume":"8","author":"JA Taylor","year":"2013","journal-title":"PLoS One"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"814","DOI":"10.2307\/3283896","article-title":"Effects of verapamil on acute murine Chagas&apos; disease","volume":"82","author":"HB Tanowitz","year":"1996","journal-title":"J Parasitol"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0020-7519(01)00320-4","article-title":"Cardioprotective effects of verapamil on myocardial structure and function in a murine model of chronic Trypanosoma cruzi infection (Brazil Strain): an echocardiographic study","volume":"32","author":"M Chandra","year":"2002","journal-title":"Int J Parasitol"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/s00436-004-1080-1","article-title":"Effects of early and late verapamil administration on the development of cardiomyopathy in experimental chronic Trypanosoma cruzi (Brazil strain) infection","volume":"92","author":"AP De Souza","year":"2004","journal-title":"Parasitol Res"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/0035-9203(92)90414-8","article-title":"Studies on a new antimalarial compound: pyronaridine","volume":"86","author":"C Chang","year":"1992","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.actatropica.2007.12.005","article-title":"Anti-malarial efficacy of pyronaridine and artesunate in combination in vitro and in vivo","volume":"105","author":"L Vivas","year":"2008","journal-title":"Acta Trop"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.bbrc.2004.05.099","article-title":"Pyronaridine, a novel modulator of P-glycoprotein-mediated multidrug resistance in tumor cells in vitro and in vivo","volume":"319","author":"J Qi","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"ref95","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1186\/1475-2875-11-270","article-title":"Review of pyronaridine anti-malarial properties and product characteristics","volume":"11","author":"SL Croft","year":"2012","journal-title":"Malar J"},{"key":"ref96","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1111\/j.1523-5378.2012.00946.x","article-title":"A modified bismuth-containing quadruple therapy including a short course of furazolidone for Helicobacter pylori eradication after sequential therapy failure","volume":"17","author":"H Fakheri","year":"2012","journal-title":"Helicobacter"},{"key":"ref97","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0035-9203(80)90010-3","article-title":"The activity against Trypanosoma cruzi and cutaneous leishmaniasis, and toxicity, of moxipraquine (349C59)","volume":"74","author":"E Beveridge","year":"1980","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ref98","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/00001813-199803000-00008","article-title":"The bisbenzylisoquinoline alkaloids, tetrandine and fangchinoline, enhance the cytotoxicity of multidrug resistance-related drugs via modulation of P-glycoprotein","volume":"9","author":"SU Choi","year":"1998","journal-title":"Anticancer Drugs"},{"key":"ref99","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1475-2875-12-117","article-title":"Effective treatment with a tetrandrine\/chloroquine combination for chloroquine-resistant falciparum malaria in Aotus monkeys","volume":"12","author":"Z Ye","year":"2013","journal-title":"Malar J"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0003878","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T22:04:47Z","timestamp":1748469887000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0003878"}},"subtitle":[],"editor":[{"given":"Frederick S","family":"Buckner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,6,26]]},"references-count":99,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2015,6,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0003878","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,26]]}}}