{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:51:33Z","timestamp":1792039893583,"version":"4.4.0"},"reference-count":222,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003329","name":"MINECO","doi-asserted-by":"publisher","award":["SAF2017-83575-R"],"award-info":[{"award-number":["SAF2017-83575-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Due to the lack of specific vaccines, management of the trypanosomatid-caused neglected tropical diseases (sleeping sickness, Chagas disease and leishmaniasis) relies exclusively on pharmacological treatments. Current drugs against them are scarce, old and exhibit disadvantages, such as adverse effects, parenteral administration, chemical instability and high costs which are often unaffordable for endemic low-income countries. Discoveries of new pharmacological entities for the treatment of these diseases are scarce, since most of the big pharmaceutical companies find this market unattractive. In order to fill the pipeline of compounds and replace existing ones, highly translatable drug screening platforms have been developed in the last two decades. Thousands of molecules have been tested, including nitroheterocyclic compounds, such as benznidazole and nifurtimox, which had already provided potent and effective effects against Chagas disease. More recently, fexinidazole has been added as a new drug against African trypanosomiasis. Despite the success of nitroheterocycles, they had been discarded from drug discovery campaigns due to their mutagenic potential, but now they represent a promising source of inspiration for oral drugs that can replace those currently on the market. The examples provided by the trypanocidal activity of fexinidazole and the promising efficacy of the derivative DNDi-0690 against leishmaniasis seem to open a new window of opportunity for these compounds that were discovered in the 1960s. In this review, we show the current uses of nitroheterocycles and the novel derived molecules that are being synthesized against these neglected diseases.<\/jats:p>","DOI":"10.3390\/biom13040637","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T03:08:31Z","timestamp":1680491311000},"page":"637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Further Investigations of Nitroheterocyclic Compounds as Potential Antikinetoplastid Drug Candidates"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5617-9669","authenticated-orcid":false,"given":"Carlos","family":"Garc\u00eda-Estrada","sequence":"first","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"P\u00e9rez-Pertejo","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara","family":"Dom\u00ednguez-Asenjo","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanderlan Nogueira","family":"Holanda","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3680-1577","authenticated-orcid":false,"given":"Sankaranarayanan","family":"Murugesan","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani 333031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3723-1895","authenticated-orcid":false,"given":"Mar\u00eda","family":"Mart\u00ednez-Valladares","sequence":"additional","affiliation":[{"name":"Instituto de Ganader\u00eda de Monta\u00f1a (IGM), Consejo Superior de Investigaciones Cient\u00edficas-Universidad de Le\u00f3n, Carretera Le\u00f3n-Vega de Infanzones, Vega de Infanzones, 24346 Le\u00f3n, Spain"},{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0418-6116","authenticated-orcid":false,"given":"Rafael","family":"Bala\u00f1a-Fouce","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9148-2997","authenticated-orcid":false,"given":"Rosa M.","family":"Reguera","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,1]]},"reference":[{"key":"ref_1","unstructured":"WHO (2020). Global leishmaniasis surveillance, 2017\u20132018, and first report on 5 additional indicators. Wkly. Epidemiol. Rec., 95, 265\u2013280."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nrmicro.2016.193","article-title":"Anti-trypanosomatid drug discovery: An ongoing challenge and a continuing need","volume":"15","author":"Field","year":"2017","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"C157","DOI":"10.12968\/hmed.2016.77.10.C157","article-title":"African sleeping sickness","volume":"77","author":"Hedley","year":"2016","journal-title":"Br. J. Hosp. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Franco, J.R., Cecchi, G., Priotto, G., Paone, M., Diarra, A., Grout, L., Simarro, P.P., Zhao, W., and Argaw, D. (2020). Monitoring the elimination of human African trypanosomiasis at continental and country level: Update to 2018. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008261"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Franco, J.R., Cecchi, G., Paone, M., Diarra, A., Grout, L., Kadima Ebeja, A., Simarro, P.P., Zhao, W., and Argaw, D. (2022). The elimination of human African trypanosomiasis: Achievements in relation to WHO road map targets for 2020. PLoS Negl. Trop. Dis., 16.","DOI":"10.1371\/journal.pntd.0010047"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hackett, F., Berrang Ford, L., F\u00e8vre, E., and Simarro, P. (2014). Incorporating scale dependence in disease burden estimates: The case of human African trypanosomiasis in Uganda. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002704"},{"key":"ref_8","unstructured":"GBD 2017 DALYs and HALE Collaborators (2018). Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet, 392, 1859\u20131922."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0140-6736(09)60829-1","article-title":"Human African trypanosomiasis","volume":"375","author":"Brun","year":"2010","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S0140-6736(17)31612-4","article-title":"Chagas disease","volume":"391","author":"Molina","year":"2018","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.idc.2018.10.015","article-title":"American trypanosomiasis (Chagas Disease)","volume":"33","author":"Morillo","year":"2019","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1590\/0074-02760140285","article-title":"Update on oral Chagas disease outbreaks in Venezuela: Epidemiological, clinical and diagnostic approaches","volume":"110","author":"Noya","year":"2011","journal-title":"Mem\u00f3rias Inst. Oswaldo Cruz"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.cmi.2017.04.013","article-title":"Challenges in the management of Chagas disease in Latin-American migrants in Europe","volume":"23","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_14","unstructured":"WHO (2015). Chagas disease in Latin America: An epidemiological update based on 2010 estimates. Wkly. Epidemiol. Rec., 6, 33\u201344."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.csbj.2016.12.002","article-title":"Chagas disease research and development: Is there light at the end of the tunnel?","volume":"15","author":"Chatelain","year":"2016","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e2015072","DOI":"10.1001\/jamanetworkopen.2020.15072","article-title":"Risk of chronic cardiomyopathy among patients with the acute phase or indeterminate form of Chagas disease: A systematic review and meta-analysis","volume":"3","author":"Chadalawada","year":"2020","journal-title":"JAMA Network Open"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00418-014-1250-x","article-title":"Chagasic megacolon: Enteric neurons and related structures","volume":"142","author":"Jabari","year":"2014","journal-title":"Histochem. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.ad.2021.02.008","article-title":"Cutaneous and mucocutaneous leishmaniasis","volume":"112","author":"Diago","year":"2021","journal-title":"Actas Dermosifiliogr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ijpddr.2019.06.003","article-title":"Route map for the discovery and pre-clinical development of new drugs and treatments for cutaneous leishmaniasis","volume":"11","author":"Caridha","year":"2019","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"756","DOI":"10.12688\/f1000research.19056.4","article-title":"Orofacial manifestations of mucocutaneous leishmaniasis: A case series from Brazil","volume":"8","author":"Sarmento","year":"2020","journal-title":"F1000Res"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.idc.2012.03.005","article-title":"Visceral leishmaniasis","volume":"26","author":"Diro","year":"2012","journal-title":"Infect. Di.s Clin. N. Am."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1111\/j.1365-4632.2010.04558.x","article-title":"Post-kala-azar dermal leishmaniasis-an overview","volume":"49","author":"Ganguly","year":"2010","journal-title":"Int. J. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e161","DOI":"10.1016\/S2214-109X(19)30538-8","article-title":"Evidence for visceral leishmaniasis elimination in Nepal","volume":"8","author":"Banjara","year":"2020","journal-title":"Lancet Glob. Health"},{"key":"ref_24","first-page":"CD003463","article-title":"Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection","volume":"2014","author":"Villar","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Malone, C.J., Nevis, I., Fern\u00e1ndez, E., and S\u00e1nchez, A. (2021). A rapid review on the efficacy and safety of pharmacological treatments for Chagas disease. Trop. Med. Infect. Dis., 6.","DOI":"10.3390\/tropicalmed6030128"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mansoldo, F.R.P., Carta, F., Angeli, A., Cardoso, V.D.S., Supuran, C.T., and Vermelho, A.B. (2020). Chagas Disease: Perspectives on the past and present and challenges in drug discovery. Molecules, 25.","DOI":"10.3390\/molecules25225483"},{"key":"ref_27","first-page":"357","article-title":"Ensaio terap\u00eautico-cl\u00ednico com benzonidazol na doenca de Chagas","volume":"18","author":"Ferreira","year":"1976","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1080\/00034983.1978.11719278","article-title":"Mode of action of the 2-nitroimidazole derivative benznidazole","volume":"72","author":"Polak","year":"1978","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Canavaci, A.M., Bustamante, J.M., Padilla, A.M., P\u00e9rez Brandan, C.M., Simpson, L.J., Xu, D., Boehlke, C.L., and Tarleton, R.L. (2010). In vitro and in vivo high-throughput assays for the testing of anti-Trypanosoma cruzi compounds. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000740"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4703","DOI":"10.1038\/srep04703","article-title":"Nitroheterocyclic compounds are more efficacious than CYP51 inhibitors against Trypanosoma cruzi: Implications for Chagas disease drug discovery and development","volume":"4","author":"Moraes","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"112047","DOI":"10.1016\/j.jinorgbio.2022.112047","article-title":"Silver and copper-benznidazole derivatives as potential antiparasitic metallodrugs: Synthesis, characterization, and biological evaluation","volume":"239","author":"Barrias","year":"2023","journal-title":"J. Inorg. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e01912","DOI":"10.1128\/AAC.01912-16","article-title":"Pharmacokinetics of benznidazole in healthy volunteers and implications in future clinical trials","volume":"61","author":"Molina","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.4269\/ajtmh.16-0761","article-title":"Experimental and clinical treatment of Chagas disease: A review","volume":"97","author":"Molina","year":"2017","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1080\/17512433.2018.1509704","article-title":"Clinical and pharmacological profile of benznidazole for treatment of Chagas disease","volume":"11","author":"Kratz","year":"2018","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Altcheh, J., Moscatelli, G., Mastrantonio, G., Moroni, S., Giglio, N., Marson, M.E., Ballering, G., Bisio, M., Koren, G., and Garc\u00eda-Bournissen, F. (2014). Population pharmacokinetic study of benznidazole in pediatric Chagas disease suggests efficacy despite lower plasma concentrations than in adults. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002907"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/bcp.14700","article-title":"Review of pharmacological options for the treatment of Chagas disease","volume":"88","author":"Lascano","year":"2022","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/S0140-6736(96)04128-1","article-title":"Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection","volume":"348","author":"Zicker","year":"1996","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"526","DOI":"10.4269\/ajtmh.1998.59.526","article-title":"Efficacy of chemotherapy with benznidazole in children in the indeterminate phase of Chagas","volume":"59","author":"Segura","year":"1998","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/jac\/dkg338","article-title":"Aetiological treatment of congenital Chagas\u2019 disease diagnosed and monitored by the polymerase chain reaction","volume":"52","author":"Schijman","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1056\/NEJMoa1313122","article-title":"Randomized trial of posaconazole and benznidazole for chronic Chagas\u2019 disease","volume":"370","author":"Molina","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_41","first-page":"939","article-title":"Benznidazole and posaconazole in eliminating parasites in asymptomatic T. cruzi carriers: The STOP-CHAGAS trial","volume":"9","author":"Morillo","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S1473-3099(17)30538-8","article-title":"Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: A proof-of-concept, randomised, placebo-controlled trial","volume":"18","author":"Torrico","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.actatropica.2017.07.004","article-title":"Prevention of congenital Chagas disease by Benznidazole treatment in reproductive-age women. An observational study","volume":"174","author":"Vigliano","year":"2017","journal-title":"Acta Trop."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1128\/AAC.01401-12","article-title":"Benznidazole-related adverse drug reactions and their relationship to serum drug concentrations in patients with chronic Chagas disease","volume":"57","author":"Pinazo","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/S1473-3099(20)30844-6","article-title":"New regimens of benznidazole monotherapy and in combination with fosravuconazole for treatment of Chagas disease (BENDITA): A phase 2, double-blind, randomised trial","volume":"21","author":"Torrico","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1186\/s13063-020-4226-2","article-title":"Efficacy and safety assessment of different dosage of benznidazol for the treatment of Chagas disease in chronic phase in adults (MULTIBENZ study): Study protocol for a multicenter randomized phase II non- inferiority clinical trial","volume":"21","author":"Sulleiro","year":"2020","journal-title":"Trials"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s12978-020-00972-1","article-title":"Short-course benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): A non-inferiority randomized controlled trial study protocol","volume":"17","author":"Cafferata","year":"2020","journal-title":"Reprod. Health"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-4274(02)00238-2","article-title":"Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems","volume":"136","author":"Diaz","year":"2002","journal-title":"Toxicol Lett"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.eimc.2020.04.011","article-title":"Trypanocidal treatment of Chagas disease","volume":"39","author":"Molina","year":"2021","journal-title":"Enferm. Infecc. Microbiol. Clin."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1191\/0960327106het653oa","article-title":"Toxic side effects of drugs used to treat CD (American trypanosomiasis)","volume":"25","author":"Castro","year":"2006","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_51","first-page":"454","article-title":"Pharmacokinetics of a nitrofuran compound, nifurtimox, in healthy volunteers","volume":"27","author":"Paulos","year":"1989","journal-title":"Int. J. Clin. Pharmacol. Ther. Toxicol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Moroni, S., Marson, M.E., Moscatelli, G., Mastrantonio, G., Bisio, M., Gonz\u00e1lez, N., Ballering, G., Altcheh, J., and Garc\u00eda-Bournissen, F. (2019). Negligible exposure to nifurtimox through breast milk during maternal treatment for Chagas Disease. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007647"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1186\/s13063-019-3423-3","article-title":"Nifurtimox versus benznidazole or placebo for asymptomatic Trypanosoma cruzi infection (Equivalence of Usual Interventions for Trypanosomiasis\u2014EQUITY): Study protocol for a randomised controlled trial","volume":"20","author":"Villar","year":"2019","journal-title":"Trials"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Altcheh, J., Castro, L., Dib, J.C., Grossmann, U., Huang, E., Moscatelli, G., Pinto Rocha, J.J., Ram\u00edrez, T.E., and CHICO Study Group (2021). Prospective, historically controlled study to evaluate the efficacy and safety of a new paediatric formulation of nifurtimox in children aged 0 to 17 years with Chagas disease one year after treatment (CHICO). PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0008912"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"586","DOI":"10.4269\/ajtmh.1996.55.586","article-title":"The efficacy of pentamidine in the treatment of early-late stage Trypanosoma brucei gambiense trypanosomiasis","volume":"55","author":"Doua","year":"1996","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Dorlo, T.P., and Kager, P.A. (2008). Pentamidine dosage: A base\/salt confusion. PLoS Negl. Trop. Dis., 2.","DOI":"10.1371\/journal.pntd.0000225"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1017\/S0031182010001137","article-title":"Chemotherapy against human African trypanosomiasis: Is there a road of success?","volume":"137","author":"Burri","year":"2010","journal-title":"Parasitology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e01168-19","DOI":"10.1128\/AAC.01168-19","article-title":"100 years of suramin","volume":"64","author":"Wiedemar","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_59","unstructured":"Cook, G., and Zumla, A. (2008). Manson\u2019s Tropical Diseases, W.B. Saunders."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Kuepfer, I., Schmid, C., Allan, M., Edielu, A., Haary, E.P., Kakembo, A., Kibona, S., Blum, J., and Burri, C. (2012). Safety and efficacy of the 10-day melarsoprol schedule for the treatment of second stage Rhodesiense sleeping sickness. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001695"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1086\/429929","article-title":"Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: Confirmation from a multinational study (Impamel II)","volume":"191","author":"Schmid","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1046\/j.1365-3156.2001.00710.x","article-title":"Clinical description of encephalopathic syndromes and risk factors for their occurrence and outcome during melarsoprol treatment of human African trypanosomiasis","volume":"6","author":"Blum","year":"2001","journal-title":"Trop. Med. Int. Health"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1007\/s00436-002-0766-5","article-title":"Eflornithine for the treatment of human African trypanosomiasis","volume":"90","author":"Burri","year":"2003","journal-title":"Parasitol. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0024-3205(94)00916-3","article-title":"Fluorinated analogues of L-ornithine are powerful inhibitors of ornithine decarboxylase and cell growth of Leishmania infantum promastigotes","volume":"56","author":"Reguera","year":"1994","journal-title":"Life Sci."},{"key":"ref_65","first-page":"CD015374","article-title":"Chemotherapy for second- stage human African trypanosomiasis: Drugs in use","volume":"12","author":"Lutje","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/0140-6736(92)92180-N","article-title":"Efficacy and toxicity of eflornithine for treatment of Trypanosoma brucei gambiense sleeping sickness","volume":"340","author":"Milord","year":"1992","journal-title":"Lancet"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Imran, M., Khan, S.A., Alshammari, M.K., Alqahtani, A.M., Alanazi, T.A., Kamal, M., Jawaid, T., Ghoneim, M.M., Alshehri, S., and Shakeel, F. (2022). Discovery, development, inventions and patent review of fexinidazole: The first all-oral therapy for human African trypanosomiasis. Pharmaceuticals, 15.","DOI":"10.3390\/ph15020128"},{"key":"ref_68","first-page":"969","article-title":"New chemotherapeutically active nitroimidazoles","volume":"2","author":"Winkelmann","year":"1980","journal-title":"Curr. Chemother. Infect. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/00034983.1983.11811668","article-title":"The activity of fexinidazole (HOE 239) against experimental infections with Trypanosoma cruzi, trichomonads and Entamoeba histolytica","volume":"77","author":"Raether","year":"1983","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/BF00926669","article-title":"The use of the 2 substituted 5-nitroimidazole, Fexinidazole (Hoe 239) in the treatment of chronic T. brucei infections in mice","volume":"69","author":"Jennings","year":"1983","journal-title":"Z. Parasitenkd."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Torreele, E., Bourdin Trunz, B., Tweats, D., Kaiser, M., Brun, R., Mazu\u00e9, G., Bray, M.A., and P\u00e9coul, B. (2010). Fexinidazole\u2014A new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000923"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1517\/14656566.2015.973850","article-title":"An update on pharmacotherapy for leishmaniasis","volume":"16","author":"Sundar","year":"2015","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s40265-019-1051-6","article-title":"Fexinidazole: First global approval","volume":"79","author":"Deeks","year":"2019","journal-title":"Drugs"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s40262-014-0136-3","article-title":"Determination of an optimal dosing regimen for fexinidazole, a novel oral drug for the treatment of human African trypanosomiasis: First-in-human studies","volume":"53","author":"Tarral","year":"2014","journal-title":"Clin. Pharmacokinet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e02515","DOI":"10.1128\/AAC.02515-18","article-title":"Pharmacokinetic-pharmacodynamic assessment of the hepatic and bone marrow toxicities of the new trypanoside fexinidazole","volume":"63","author":"Watson","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5602","DOI":"10.1128\/AAC.00246-11","article-title":"Antitrypanosomal activity of fexinidazole, a new oral nitroimidazole drug candidate for treatment of sleeping sickness","volume":"55","author":"Kaiser","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ijantimicag.2017.01.038","article-title":"Dose-dependent effect and pharmacokinetics of fexinidazole and its metabolites in a mouse model of human African trypanosomiasis","volume":"50","author":"Harris","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S0140-6736(17)32758-7","article-title":"Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: A pivotal multicentre, randomised, non-inferiority trial","volume":"391","author":"Mesu","year":"2018","journal-title":"Lancet"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e999","DOI":"10.1016\/S2214-109X(21)00208-4","article-title":"Oral fexinidazole for stage 1 or early stage 2 African Trypanosoma brucei gambiense trypanosomiasis: A prospective, multicentre, open-label, cohort study","volume":"9","author":"Mesu","year":"2021","journal-title":"Lancet Glob. Health"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Neau, P., H\u00e4nel, H., Lameyre, V., Strub-Wourgaft, N., and Kuykens, L. (2020). Innovative partnerships for the elimination of Human African Trypanosomiasis and the development of fexinidazole. Trop. Med. Infect. Dis., 5.","DOI":"10.3390\/tropicalmed5010017"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1016\/S1473-3099(19)30612-7","article-title":"New WHO guidelines for treatment of gambiense human African trypanosomiasis including fexinidazole: Substantial changes for clinical practice","volume":"20","author":"Lindner","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Yun, O., Priotto, G., Tong, J., Flevaud, L., and Chappuis, F. (2010). NECT is next: Implementing the new drug combination therapy for Trypanosoma brucei gambiense sleeping sickness. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000720"},{"key":"ref_83","unstructured":"WHO (2023, March 03). Model Lists of Essential Medicines, 16th List. Available online: http:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/70643\/a95060_eng.pdf?sequence=1."},{"key":"ref_84","unstructured":"WHO (2023, March 03). Model Lists of Essential Medicines for Children, 4th List. Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/93143\/EMLc_4_eng.pdf;jsessionid=5BAB0668B5399535021865B2635D8883?sequence=1."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0140-6736(09)61117-X","article-title":"Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: A multicentre, randomised, phase III, non-inferiority trial","volume":"374","author":"Priotto","year":"2009","journal-title":"Lancet"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s13071-018-2634-x","article-title":"A multicentre, randomised, non-inferiority clinical trial comparing a nifurtimox-eflornithine combination to standard eflornithine monotherapy for late-stage Trypanosoma brucei gambiense human African trypanosomiasis in Uganda","volume":"11","author":"Kansiime","year":"2018","journal-title":"Parasites Vectors"},{"key":"ref_87","unstructured":"WHO (2019). Model List of Essential Medicines: 21st List 2019, World Health Organization. Available online: https:\/\/www.who.int\/publications\/i\/item\/WHOMVPEMPIAU2019.06."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1124\/jpet.110.172981","article-title":"The distribution of nifurtimox across the healthy and trypanosome-infected murine blood-brain and blood-cerebrospinal fluid barriers","volume":"336","author":"Jeganathan","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1179\/2047773213Y.0000000105","article-title":"A current analysis of chemotherapy strategies for the treatment of human African trypanosomiasis","volume":"107","author":"Babokhov","year":"2013","journal-title":"Pathog. Glob. Health"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Schmid, C., Kuemmerle, A., Blum, J., Ghabri, S., Kande, V., Mutombo, W., Ilunga, M., Lumpungu, I., Mutanda, S., and Nganzobo, P. (2012). In-hospital safety in field conditions of nifurtimox eflornithine combination therapy (NECT) for T. b. gambiense sleeping sickness. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001920"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Kuemmerle, A., Schmid, C., Bernhard, S., Kande, V., Mutombo, W., Ilunga, M., Lumpungu, I., Mutanda, S., Nganzobo, P., and Tete, D.N. (2021). Effectiveness of Nifurtimox Eflornithine Combination Therapy (NECT) in T. b. gambiense second stage sleeping sickness patients in the Democratic Republic of Congo: Report from a field study. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009903"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.3390\/molecules14072317","article-title":"Pentavalent antimonials: New perspectives for old drugs","volume":"14","author":"Demicheli","year":"2009","journal-title":"Molecules"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1074\/jbc.M005423200","article-title":"Novel intracellular SbV reducing activity correlates with antimony susceptibility in Leishmania donovani","volume":"276","author":"Ulrich","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1517\/14656566.2013.755515","article-title":"Leishmaniasis: An update of current pharmacotherapy","volume":"14","author":"Sundar","year":"2013","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Zijlstra, E.E., Alves, F., Rijal, S., Arana, B., and Alvar, J. (2017). Post-kala-azar dermal leishmaniasis in the Indian subcontinent: A threat to the South-East Asia Region Kala-azar Elimination Programme. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005877"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.3390\/ijerph7124267","article-title":"Antimony toxicity","volume":"7","author":"Sundar","year":"2010","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1128\/AAC.01298-10","article-title":"High mortality among older patients treated with pentavalent antimonials for visceral leishmaniasis in East Africa and rationale for switch to liposomal amphotericin B","volume":"55","author":"Chappuis","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1056\/NEJMoa0903627","article-title":"Single-dose liposomal amphotericin B for visceral leishmaniasis in India","volume":"362","author":"Sundar","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"795","DOI":"10.4269\/ajtmh.19-0179","article-title":"Effectiveness of single-dose liposomal amphotericin b in visceral leishmaniasis in Bihar","volume":"101","author":"Sundar","year":"2019","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/0378-5173(88)90107-X","article-title":"A stability study of amphotericin B in aqueous media using factorial design","volume":"44","author":"Hung","year":"1988","journal-title":"Int. J. Pharm."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1017\/S0031182017002116","article-title":"Chemotherapeutics of visceral leishmaniasis: Present and future developments","volume":"145","author":"Sundar","year":"2018","journal-title":"Parasitology"},{"key":"ref_102","first-page":"106459","article-title":"An update on the clinical pharmacology of miltefosine in the treatment of leishmaniasis","volume":"22","author":"Beijnen","year":"2021","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1517\/14656566.6.8.1381","article-title":"Miltefosine to treat leishmaniasis","volume":"6","author":"Berman","year":"2005","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1128\/AAC.00292-12","article-title":"Optimal dosing of miltefosine in children and adults with visceral leishmaniasis","volume":"56","author":"Dorlo","year":"2012","journal-title":"Antimicrob Agents Chemother."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.trstmh.2006.02.010","article-title":"Development of miltefosine as an oral treatment for leishmaniasis","volume":"100","author":"Sindermann","year":"2006","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Hailu, A., Musa, A., Wasunna, M., Balasegaram, M., Yifru, S., Mengistu, G., Hurissa, Z., Hailu, W., Weldegebreal, T., and Tesfaye, S. (2010). Geographical variation in the response of visceral leishmaniasis to paromomycin in East Africa: A multicentre, open-label, randomized trial. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000709"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Musa, A., Khalil, E., Hailu, A., Olobo, J., Balasegaram, M., Omollo, R., Edwards, T., Rashid, J., Mbui, J., and Musa, B. (2012). Sodium stibogluconate (SSG) & paromomycin combination compared to SSG for visceral leishmaniasis in East Africa: A randomised controlled trial. PLos Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001674"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1093\/femsre\/fuw018","article-title":"Alice in microbes\u2019 land: Adaptations and counter-adaptations of vector-borne parasitic protozoa and their hosts","volume":"40","author":"Caljon","year":"2016","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/s41579-019-0238-x","article-title":"Protozoan persister-like cells and drug treatment failure","volume":"17","author":"Barrett","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Bhattacharya, A., Corbeil, A., do Monte-Neto, R.L., and Fernandez-Prada, C. (2020). Of drugs and trypanosomatids: New tools and knowledge to reduce bottlenecks in drug discovery. Genes, 11.","DOI":"10.3390\/genes11070722"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Perry, M.R., Wyllie, S., Prajapati, V.K., Feldmann, J., Sundar, S., Boelaert, M., and Fairlamb, A.H. (2011). Visceral leishmaniasis and arsenic: An ancient poison contributing to antimonial treatment failure in the Indian subcontinent?. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001227"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Mandal, G., Mandal, S., Sharma, M., Charret, K.S., Papadopoulou, B., Bhattacharjee, H., and Mukhopadhyay, R. (2015). Species-specific antimonial sensitivity in Leishmania is driven by post-transcriptional regulation of AQP1. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003500"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.pt.2018.04.002","article-title":"Melarsoprol Resistance in African Trypanosomiasis","volume":"34","author":"Fairlamb","year":"2018","journal-title":"Trends Parasitol."},{"key":"ref_114","first-page":"49965","article-title":"Functional cloning of the miltefosine transporter. A novel P-type phospholipid translocase from Leishmania involved in drug resistance","volume":"278","author":"Gamarro","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"De Koning, P.H. (2020). The drugs of sleeping sickness: Their mechanisms of action and resistance, and a brief history. Trop. Med. Infect. Dis., 5.","DOI":"10.3390\/tropicalmed5010014"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/0006-2952(93)90524-Z","article-title":"Resistance to DL-\u03b1-difluoromethylornithine by clinical isolates of Trypanosoma brucei rhodesiense. Role of S-adenosylmethionine","volume":"46","author":"Bacchi","year":"1993","journal-title":"Biochem. Pharmacol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.cca.2005.02.006","article-title":"Polyamine transport in parasites: A potential target for new antiparasitic drug development","volume":"140","author":"Reguera","year":"2005","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"13088","DOI":"10.1074\/jbc.M111.230847","article-title":"Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites","volume":"286","author":"Hall","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1128\/AAC.00332-10","article-title":"Cross-resistance to nitro drugs and implications for treatment of human African trypanosomiasis","volume":"54","author":"Sokolova","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Alpizar-Sosa, E.A., Ithnin, N.R.B., Wei, W., Pountain, A.W., Weidt, S.K., Donachie, A.M., Ritchie, R., Dickie, E.A., Burchmore, R.J.S., and Denny, P.W. (2022). Amphotericin B resistance in Leishmania mexicana: Alterations to sterol metabolism and oxidative stress response. PLoS Negl. Trop. Dis., 16.","DOI":"10.1371\/journal.pntd.0010779"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1017\/S0031182017001469","article-title":"Biological factors that impinge on Chagas disease drug development","volume":"144","author":"Francisco","year":"2017","journal-title":"Parasitology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.pt.2013.12.004","article-title":"Post kala-azar dermal leishmaniasis: An unresolved mystery","volume":"30","author":"Mukhopadhyay","year":"2014","journal-title":"Trends Parasitol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/s42003-022-03591-7","article-title":"Long-term hematopoietic stem cells as a parasite niche during treatment failure in visceral leishmaniasis","volume":"5","author":"Dirkx","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.2217\/fmb.15.68","article-title":"Using combination therapy to thwart drug resistance","volume":"10","author":"Hill","year":"2015","journal-title":"Future Microbiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e00048-18","DOI":"10.1128\/CMR.00048-18","article-title":"Recent development of visceral leishmaniasis treatments: Successes, pitfalls, and perspectives","volume":"31","author":"Alves","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.drudis.2019.03.007","article-title":"Walking a tightrope: Drug discovery in visceral leishmaniasis","volume":"24","author":"Reguera","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_127","first-page":"6185","article-title":"Spotlight on tavaborole for the treatment of onychomycosis","volume":"9","author":"Jinna","year":"2015","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Dickie, E.A., Giordani, F., Gould, M.K., M\u00e4ser, P., Burri, C., Mottram, J.C., Rao, S.P.S., and Barrett, M.P. (2020). New drugs for human African trypanosomiasis: A twenty first century success story. Trop. Med. Infect. Dis., 5.","DOI":"10.3390\/tropicalmed5010029"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ijpddr.2019.02.002","article-title":"Novel benzoxaborole, nitroimidazole and aminopyrazoles with activity against experimental cutaneous leishmaniasis","volume":"11","author":"Caridha","year":"2019","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"16159","DOI":"10.1021\/acs.jmedchem.1c01437","article-title":"DNDI-6148: A novel benzoxaborole preclinical candidate for the treatment of visceral leishmaniasis","volume":"64","author":"Mowbray","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/17460441.2020.1681394","article-title":"Why hasn\u2019t there been more progress in new Chagas disease drug discovery?","volume":"15","author":"Vermelho","year":"2020","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1038\/s41564-022-01211-y","article-title":"Discovery of an orally active benzoxaborole prodrug effective in the treatment of Chagas disease in non-human primates","volume":"7","author":"Padilla","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1002\/cmdc.201300072","article-title":"From on-target to off-target activity: Identification and optimisation of Trypanosoma brucei GSK3 inhibitors and their characterisation as anti-Trypanosoma brucei drug discovery lead molecules","volume":"8","author":"Woodland","year":"2013","journal-title":"ChemMedChem"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/s41586-018-0356-z","article-title":"Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis","volume":"560","author":"Wyllie","year":"2018","journal-title":"Nature"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1021\/acs.jmedchem.8b01218","article-title":"Identification of GSK3186899\/DDD853651 as a preclinical development candidate for the treatment of visceral leishmaniasis","volume":"62","author":"Thomas","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_136","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":"Khare","year":"2016","journal-title":"Nature"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"10773","DOI":"10.1021\/acs.jmedchem.0c00499","article-title":"Discovery and characterization of clinical candidate LXE408 as a kinetoplastid-selective proteasome inhibitor for the treatment of leishmaniases","volume":"63","author":"Nagle","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"9318","DOI":"10.1073\/pnas.1820175116","article-title":"Preclinical candidate for the treatment of visceral leishmaniasis that acts through proteasome inhibition","volume":"116","author":"Wyllie","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1002\/1521-4141(200209)32:9<2617::AID-IMMU2617>3.0.CO;2-F","article-title":"CpG oligodeoxynucleotides induce human monocytes to mature into functional dendritic cells","volume":"32","author":"Gursel","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Thacker, S.G., McWilliams, I.L., Bonnet, B., Halie, L., Beaucage, S., Rachuri, S., Dey, R., Duncan, R., Modabber, F., and Robinson, S. (2020). CpG ODN D35 improves the response to abbreviated low-dose pentavalent antimonial treatment in non-human primate model of cutaneous leishmaniasis. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008050"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.pt.2014.04.003","article-title":"Nitro drugs for the treatment of trypanosomatid diseases: Past, present, and future prospects","volume":"30","author":"Patterson","year":"2014","journal-title":"Trends Parasitol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/cmdc.200700139","article-title":"Lessons learnt from assembling screening libraries for drug discovery for neglected diseases","volume":"3","author":"Brenk","year":"2008","journal-title":"ChemMedChem"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1021\/acsinfecdis.1c00139","article-title":"Ex vivo phenotypic screening of two small repurposing drug collections identifies nifuratel as a potential new treatment against visceral and cutaneous leishmaniasis","volume":"7","author":"Reguera","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"128930","DOI":"10.1016\/j.bmcl.2022.128930","article-title":"Nitro compounds against trypanosomatidae parasites: Heroes or villains?","volume":"75","year":"2022","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Thomas, C., and Gwenin, C.D. (2021). The role of nitroreductases in resistance to nitroimidazoles. Biology, 10.","DOI":"10.3390\/biology10050388"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"20388","DOI":"10.1038\/s41598-022-23941-z","article-title":"Fexinidazole interferes with the growth and structural organization of Trypanosoma cruzi","volume":"12","author":"Zuma","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Bahia, M.T., de Andrade, I.M., Martins, T.A., do Nascimento, \u00c1.F., Diniz Lde, F., Caldas, I.S., Talvani, A., Trunz, B.B., Torreele, E., and Ribeiro, I. (2012). Fexinidazole: A potential new drug candidate for Chagas disease. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001870"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"4362","DOI":"10.1128\/AAC.02754-13","article-title":"Antitrypanosomal activity of fexinidazole metabolites, potential new drug candidates for Chagas disease","volume":"58","author":"Bahia","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"35351","DOI":"10.1038\/srep35351","article-title":"Nitroheterocyclic drugs cure experimental Trypanosoma cruzi infections more effectively in the chronic stage than in the acute stage","volume":"6","author":"Francisco","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"119re1","DOI":"10.1126\/scitranslmed.3003326","article-title":"The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis","volume":"4","author":"Wyllie","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1093\/jac\/dkz172","article-title":"In vitro activity and in vivo efficacy of fexinidazole against New World Leishmania species","volume":"74","author":"Rabello","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1590\/S0037-86821970000300003","article-title":"Tratamento, pelo metronidazol, de pacientes com a forma cr\u00f4nica da doen\u00e7a de Chagas","volume":"4","author":"Levi","year":"1970","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_153","first-page":"5","article-title":"Forma aguda de la enfermedad de Chagas, importancia semiol\u00f3gica del Signo de Romana\u2014Informe de los dos primeros casos en Honduras","volume":"39","year":"1971","journal-title":"Med. Hondur."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bcp.2017.08.025","article-title":"Drug repurposing strategy against Trypanosoma cruzi infection: In vitro and in vivo assessment of the activity of metronidazole in mono- and combined therapy","volume":"145","author":"Oliveira","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_155","first-page":"1512","article-title":"Treatment of cutaneous leishmaniasis by intralesional metronidazole","volume":"25","author":"Sharquie","year":"2004","journal-title":"Saudi Med. J."},{"key":"ref_156","first-page":"257","article-title":"Intralesional pentostam versus intralesional metronidazole in treating cutaneous leishmaniasis: A comparison study","volume":"23","author":"Bahman","year":"2019","journal-title":"Zanco J. Med. Sci."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/09546634.2018.1472738","article-title":"Randomized, double-blind study on intralesional metronidazole versus intralesional sodium stibogluconate in Leishmania donovani cutaneous leishmaniasis","volume":"30","author":"Somaratne","year":"2019","journal-title":"J. Dermatolog. Treat."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"5655","DOI":"10.1021\/acs.jmedchem.9b00628","article-title":"Synthesis, biological evaluation, structure- activity relationship, and mechanism of action studies of quinoline-metronidazole derivatives against experimental visceral leishmaniasis","volume":"62","author":"Upadhyay","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1007\/s40265-019-01207-9","article-title":"Pretomanid: First approval","volume":"79","author":"Keam","year":"2019","journal-title":"Drugs"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"4699","DOI":"10.1128\/AAC.00722-13","article-title":"The R enantiomer of the antitubercular drug PA-824 as a potential oral treatment for visceral leishmaniasis","volume":"57","author":"Patterson","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ijpddr.2018.01.006","article-title":"In vitro and in vivo pharmacodynamics of three novel antileishmanial lead series","volume":"8","author":"Mabille","year":"2018","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1021\/acs.jmedchem.7b01581","article-title":"Development of (6 R)-2-nitro-6-[4-(trifluoromethoxy)-phenoxy]-6,7-dihydro-5H-imidazo-[2,1-b][1,3]-oxazine (DNDI-8219): A new lead for visceral leishmaniasis","volume":"61","author":"Thompson","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"112849","DOI":"10.1016\/j.ejmech.2020.112849","article-title":"Re-evaluating pretomanid analogues for Chagas disease: Hit-to-lead studies reveal both in vitro and in vivo trypanocidal efficacy","volume":"207","author":"Thompson","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s40265-014-0241-5","article-title":"Delamanid: First global approval","volume":"74","author":"Ryan","year":"2014","journal-title":"Drugs"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"e09744","DOI":"10.7554\/eLife.09744","article-title":"The anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis","volume":"5","author":"Patterson","year":"2016","journal-title":"Elife"},{"key":"ref_166","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":"Gupta","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1021\/acs.jmedchem.5b01699","article-title":"Repositioning antitubercular 6-nitro-2,3-dihydroimidazo-[2,1-b][1,3]-oxazoles for Neglected Tropical Diseases: Structure-activity studies on a preclinical candidate for visceral leishmaniasis","volume":"59","author":"Thompson","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"e00829-19","DOI":"10.1128\/AAC.00829-19","article-title":"Pharmacokinetics and pharmacodynamics of the nitroimidazole DNDi-0690 in mouse models of cutaneous leishmaniasis","volume":"63","author":"Wijnant","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"4212","DOI":"10.1021\/acs.jmedchem.7b00034","article-title":"7-substituted-2-nitro-5,6-dihydroimidazo-[2,1-b][1,3]-oxazines: Novel antitubercular agents lead to a new preclinical candidate for visceral leishmaniasis","volume":"60","author":"Thompson","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Van Bocxlaer, K., McArthur, K.N., Harris, A., Alavijeh, M., Braillard, S., Mowbray, C.E., and Croft, S.L. (2021). Film-forming systems for the delivery of DNDI-0690 to treat cutaneous leishmaniasis. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13040516"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"112914","DOI":"10.1016\/j.ejmech.2020.112914","article-title":"Heteroaryl ether analogues of an antileishmanial 7-substituted-2-nitroimidazo oxazine lead afford attenuated hERG risk: In vitro and in vivo appraisal","volume":"209","author":"Thompson","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.freeradbiomed.2007.12.013","article-title":"Role of cytochrome P450 reductase in nitrofurantoin-induced redox cycling and cytotoxicity","volume":"44","author":"Wang","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1128\/AAC.01213-09","article-title":"Exploiting the drug-activating properties of a novel trypanosomal nitroreductase","volume":"54","author":"Hall","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"105092","DOI":"10.1016\/j.ejps.2019.105092","article-title":"An update on derivatisation and repurposing of clinical nitrofuran drugs","volume":"140","author":"Zuma","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1146\/annurev.mi.49.100195.002515","article-title":"Biodegradation of nitroaromatic compounds","volume":"49","author":"Spain","year":"1995","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s11094-005-0161-5","article-title":"Hydrolytic and reductive transformations of nifuroxazide","volume":"39","author":"Trukhacheva","year":"2005","journal-title":"Pharm. Chem. J."},{"key":"ref_177","unstructured":"Bennett, J.E., and Blaser, M.J. (2015). Mandell, Douglas, and Bennett\u2019s Principles and Practice of Infectious Diseases, Elsevier. [8th ed.]."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0014-4894(75)90020-X","article-title":"Trypanosoma cruzi: Antimicrobial activity and strain differentiating properties of some five- and six-membered heterocyclic compounds on trypomastigotes","volume":"38","author":"Freeman","year":"1975","journal-title":"Exp. Parasitol."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Munsimbwe, L., Seetsi, A., Namangala, B., N\u2019Da, D.D., Inoue, N., and Suganuma, K. (2021). In vitro and in vivo trypanocidal efficacy of synthesized nitrofurantoin analogs. Molecules, 26.","DOI":"10.3390\/molecules26113372"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Suganuma, K., N\u2019Da, D.D., Watanabe, K.I., Tanaka, Y., Mossaad, E., Elata, A., Inoue, N., and Kawazu, S.I. (2022). Therapeutic efficacy of orally administered nitrofurantoin against animal African trypanosomosis caused by Trypanosoma congolense infection. Pathogens, 11.","DOI":"10.3390\/pathogens11030331"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/00004630-199503000-00002","article-title":"Cytotoxicity testing of topical antimicrobial agents on human keratinocytes and fibroblasts for cultured skin grafts","volume":"16","author":"Boyce","year":"1995","journal-title":"J. Burn Care Rehabil."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/srep00063","article-title":"Activation of nitrofurazone by azoreductases: Multiple activities in one enzyme","volume":"1","author":"Ryan","year":"2011","journal-title":"Sci. Rep."},{"key":"ref_183","first-page":"222","article-title":"Action of nitrofurazone (5-nitro-2-furaldehyde-semicarbazone) on the intracellular forms of Trypanosoma intracellular forms of Trypanosoma cruzi in experimental Chagas\u2019 disease","volume":"11","author":"Andrade","year":"1969","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"4779","DOI":"10.1016\/j.bmc.2003.07.004","article-title":"Synthesis and in vitro evaluation of potential antichagasic hydroxymethylnitrofurazone (NFOH-121): A new nitrofurazone prodrug","volume":"11","author":"Chung","year":"2003","journal-title":"Bioorg. Med. Chem."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1016\/S0960-894X(02)00788-6","article-title":"Antitrypanosomal activities and cytotoxicity of 5-nitro-2-furancarbohydrazides","volume":"12","author":"Millet","year":"2002","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1021\/jm0512241","article-title":"Novel antitrypanosomal agents based on palladium nitrofurylthiosemicarbazone complexes: DNA and redox metabolism as potential therapeutic targets","volume":"49","author":"Otero","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1128\/AAC.48.5.1733-1738.2004","article-title":"Trypanocidal activity of melamine-based nitroheterocycles","volume":"48","author":"Stewart","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"5570","DOI":"10.1021\/jm050177+","article-title":"Design and synthesis of a series of melamine-based nitroheterocycles with activity against trypanosomatid parasites","volume":"48","author":"Baliani","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"5747","DOI":"10.1128\/AAC.01449-13","article-title":"Characterization of a melamino nitroheterocycle as a potential lead for the treatment of human African trypanosomiasis","volume":"58","author":"Giordani","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"4885","DOI":"10.1016\/j.bmc.2004.07.003","article-title":"In vitro activity and mechanism of action against the protozoan parasite Trypanosoma cruzi of 5-nitrofuryl containing thiosemicarbazones","volume":"12","author":"Aguirre","year":"2004","journal-title":"Bioorg. Med. Chem."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1128\/AAC.02046-12","article-title":"Evaluating 5-nitrofurans as trypanocidal agents","volume":"57","author":"Bot","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.exppara.2016.01.007","article-title":"Effects of nitro-heterocyclic derivatives against Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes","volume":"163","author":"Tavares","year":"2016","journal-title":"Exp. Parasitol."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Calvo-\u00c1lvarez, E., Stamatakis, K., Punz\u00f3n, C., \u00c1lvarez-Velilla, R., Tejer\u00eda, A., Escudero-Mart\u00ednez, J.M., P\u00e9rez-Pertejo, Y., Fresno, M., Bala\u00f1a-Fouce, R., and Reguera, R.M. (2015). Infrared fluorescent imaging as a potent tool for in vitro, ex vivo and in vivo models of visceral leishmaniasis. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003666"},{"key":"ref_194","first-page":"331","article-title":"Nifuratel (Magmilor) in trichomonal vaginitis","volume":"44","author":"Fowler","year":"1968","journal-title":"Br. J. Vener. Dis."},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Melc\u00f3n-Fernandez, E., Galli, G., Garc\u00eda-Estrada, C., Bala\u00f1a-Fouce, R., Reguera, R.M., and P\u00e9rez-Pertejo, Y. (2023). Miltefosine and Nifuratel Combination: A Promising Therapy for the Treatment of Leishmania donovani Visceral Leishmaniasis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021635"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"4506","DOI":"10.1016\/j.bmcl.2012.06.004","article-title":"Discovery of nitroheterocycles active against African trypanosomes. In vitro screening and prelimiary SAR studies","volume":"22","author":"Kaiser","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"28466","DOI":"10.1074\/jbc.M113.494781","article-title":"An essential type I nitroreductase from Leishmania major can be used to activate leishmanicidal prodrugs","volume":"288","author":"Voak","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"6467","DOI":"10.1016\/j.bmc.2015.08.014","article-title":"Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation","volume":"23","author":"Papadopoulou","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_199","first-page":"1137","article-title":"Evaluating 5-nitrothiazoles as trypanocidal agents","volume":"60","author":"Shahed","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"112668","DOI":"10.1016\/j.ejmech.2020.112668","article-title":"Antikinetoplastid SAR study in 3-nitroimidazopyridine series: Identification of a novel non-genotoxic and potent anti-T. b. brucei hit-compound with improved pharmacokinetic properties","volume":"206","author":"Fersing","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1128\/AAC.05135-11","article-title":"Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation","volume":"5","author":"Hall","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1023\/A:1015988401601","article-title":"Evidence for the involvement of a nitrenium ion in the covalent binding of nitrofurazone to DNA","volume":"5","author":"Streeter","year":"1988","journal-title":"Pharm. Res."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/cmdc.200900499","article-title":"The tunable functionality of \u03b1,\u03b2-unsaturated carbonyl compounds enables their differential application in biological systems","volume":"5","author":"Amslinger","year":"2010","journal-title":"ChemMedChem"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1128\/AAC.01788-12","article-title":"Assessing the essentiality of Leishmania donovani nitroreductase and its role in nitro drug activation","volume":"57","author":"Wyllie","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.ejmech.2016.10.055","article-title":"Rational design of nitrofuran derivatives: Synthesis and valuation as inhibitors of Trypanosoma cruzi trypanothione reductase","volume":"125","author":"Arias","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"4009","DOI":"10.1016\/S0021-9258(18)50687-6","article-title":"Oxygen-sensitive and\u2014Insensitive nitroreduction by Escherichia coli and rat hepatic microsomes","volume":"254","author":"Peterson","year":"1979","journal-title":"J. Biol. Chem."},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Olender, D., \u017bwawiak, J., and Zaprutko, L. (2018). Multidirectional efficacy of biologically active nitro compounds included in medicines. Pharmaceuticals, 11.","DOI":"10.3390\/ph11020054"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/S0006-2952(02)01663-5","article-title":"Trypanosoma cruzi: Effect and mode of action of nitroimidazole and nitrofuran derivatives","volume":"65","author":"Maya","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"5022","DOI":"10.1073\/pnas.0711014105","article-title":"A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes","volume":"105","author":"Wilkinson","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/j.bcp.2010.02.009","article-title":"Mode of action of nifurtimox and N-oxide-containing heterocycles against Trypanosoma cruzi: Is oxidative stress involved?","volume":"79","author":"Boiani","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.2174\/0929867311320210005","article-title":"Trypanosomatidae diseases: From the current therapy to the efficacious role of trypanothione reductase in drug discovery","volume":"20","author":"Bernardes","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Wyllie, S., Roberts, A.J., Norval, S., Patterson, S., Foth, B.J., Berriman, M., Read, K.D., and Fairlamb, A.H. (2016). Activation of bicyclic nitro-drugs by a novel nitroreductase (NTR2) in Leishmania. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005971"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1099\/00221287-148-6-1607","article-title":"\u2018New uses for an Old Enzyme\u2019\u2014The Old Yellow Enzyme family of flavoenzymes","volume":"148","author":"Williams","year":"2002","journal-title":"Microbiology"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.cbpa.2007.02.025","article-title":"Asymmetric bioreduction of activated C=C bonds using enoate reductases from the old yellow enzyme family","volume":"11","author":"Stuermer","year":"2007","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.cbpa.2014.01.019","article-title":"New developments in \u2018ene\u2019-reductase catalysed biological hydrogenations","volume":"19","author":"Toogood","year":"2014","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3389\/fimmu.2018.00456","article-title":"Old yellow enzyme from Trypanosoma cruzi exhibits in vivo prostaglandin F2\u03b1 synthase activity and has a key role in parasite infection and drug susceptibility","volume":"9","author":"Chiribao","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"170773","DOI":"10.1098\/rsos.170773","article-title":"Prostaglandin F2\u03b1 synthase in Trypanosoma cruzi plays critical roles in oxidative stress and susceptibility to benznidazole","volume":"4","author":"Machado","year":"2017","journal-title":"R. Soc. Open Sci."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1111\/mmi.14763","article-title":"Unraveling the antitrypanosomal mechanism of benznidazole and related 2-nitroimidazoles: From prodrug activation to DNA damage","volume":"116","author":"Dattani","year":"2021","journal-title":"Mol. Microbiol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.saa.2010.12.017","article-title":"ESR, electrochemical, molecular modeling and biological evaluation of 4-substituted and 1,4-disubstituted 7-nitroquinoxalin-2-ones as potential anti-Trypanosoma cruzi agents","volume":"78","author":"Norambuena","year":"2011","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"5374","DOI":"10.1073\/pnas.85.15.5374","article-title":"\u201cSubversive\u201d substrates for the enzyme trypanothione disulfide reductase: Alternative approach to chemotherapy of Chagas disease","volume":"85","author":"Henderson","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ejmech.2013.12.025","article-title":"New perspectives on the synthesis and antichagasic activity of 3-alkoxy-1-alkyl-5-nitroindazoles","volume":"74","author":"Muro","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nature10771","article-title":"High-throughput decoding of antitrypanosomal drug efficacy and resistance","volume":"482","author":"Alsford","year":"2012","journal-title":"Nature"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/4\/637\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:08:12Z","timestamp":1760123292000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/4\/637"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,1]]},"references-count":222,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["biom13040637"],"URL":"https:\/\/doi.org\/10.3390\/biom13040637","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,1]]}}}