{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T23:54:27Z","timestamp":1768002867939,"version":"3.49.0"},"reference-count":63,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Economia, Industria y Competitividad","award":["CSD2010\u201300065"],"award-info":[{"award-number":["CSD2010\u201300065"]}]},{"name":"Ministerio de Economia, Industria y Competitividad","award":["CTQ2017\u201390852-REDC"],"award-info":[{"award-number":["CTQ2017\u201390852-REDC"]}]},{"name":"Ministerio de Economia, Industria y Competitividad","award":["PID2019-110751RB-I00"],"award-info":[{"award-number":["PID2019-110751RB-I00"]}]},{"name":"Ministerio de Economia, Industria y Competitividad","award":["RED2018-102331-T"],"award-info":[{"award-number":["RED2018-102331-T"]}]},{"name":"Ministerio de Economia, Industria y Competitividad","award":["CEX2019-000919-M"],"award-info":[{"award-number":["CEX2019-000919-M"]}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Economia, Industria y Competitividad","doi-asserted-by":"publisher","award":["CSD2010\u201300065"],"award-info":[{"award-number":["CSD2010\u201300065"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Economia, Industria y Competitividad","doi-asserted-by":"publisher","award":["CTQ2017\u201390852-REDC"],"award-info":[{"award-number":["CTQ2017\u201390852-REDC"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Economia, Industria y Competitividad","doi-asserted-by":"publisher","award":["PID2019-110751RB-I00"],"award-info":[{"award-number":["PID2019-110751RB-I00"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Economia, Industria y Competitividad","doi-asserted-by":"publisher","award":["RED2018-102331-T"],"award-info":[{"award-number":["RED2018-102331-T"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Economia, Industria y Competitividad","doi-asserted-by":"publisher","award":["CEX2019-000919-M"],"award-info":[{"award-number":["CEX2019-000919-M"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MINECO and FEDER funds","award":["CSD2010\u201300065"],"award-info":[{"award-number":["CSD2010\u201300065"]}]},{"name":"MINECO and FEDER funds","award":["CTQ2017\u201390852-REDC"],"award-info":[{"award-number":["CTQ2017\u201390852-REDC"]}]},{"name":"MINECO and FEDER funds","award":["PID2019-110751RB-I00"],"award-info":[{"award-number":["PID2019-110751RB-I00"]}]},{"name":"MINECO and FEDER funds","award":["RED2018-102331-T"],"award-info":[{"award-number":["RED2018-102331-T"]}]},{"name":"MINECO and FEDER funds","award":["CEX2019-000919-M"],"award-info":[{"award-number":["CEX2019-000919-M"]}]},{"DOI":"10.13039\/501100003329","name":"MINECO and FEDER funds","doi-asserted-by":"publisher","award":["CSD2010\u201300065"],"award-info":[{"award-number":["CSD2010\u201300065"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"MINECO and FEDER funds","doi-asserted-by":"publisher","award":["CTQ2017\u201390852-REDC"],"award-info":[{"award-number":["CTQ2017\u201390852-REDC"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"MINECO and FEDER funds","doi-asserted-by":"publisher","award":["PID2019-110751RB-I00"],"award-info":[{"award-number":["PID2019-110751RB-I00"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"MINECO and FEDER funds","doi-asserted-by":"publisher","award":["RED2018-102331-T"],"award-info":[{"award-number":["RED2018-102331-T"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"MINECO and FEDER funds","doi-asserted-by":"publisher","award":["CEX2019-000919-M"],"award-info":[{"award-number":["CEX2019-000919-M"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MINECO and FEDER funds","award":["CSD2010\u201300065"],"award-info":[{"award-number":["CSD2010\u201300065"]}]},{"name":"MINECO and FEDER funds","award":["CTQ2017\u201390852-REDC"],"award-info":[{"award-number":["CTQ2017\u201390852-REDC"]}]},{"name":"MINECO and FEDER funds","award":["PID2019-110751RB-I00"],"award-info":[{"award-number":["PID2019-110751RB-I00"]}]},{"name":"MINECO and FEDER funds","award":["RED2018-102331-T"],"award-info":[{"award-number":["RED2018-102331-T"]}]},{"name":"MINECO and FEDER funds","award":["CEX2019-000919-M"],"award-info":[{"award-number":["CEX2019-000919-M"]}]},{"name":"Alfonso Mart\u00edn Escudero Foundation","award":["CSD2010\u201300065"],"award-info":[{"award-number":["CSD2010\u201300065"]}]},{"name":"Alfonso Mart\u00edn Escudero Foundation","award":["CTQ2017\u201390852-REDC"],"award-info":[{"award-number":["CTQ2017\u201390852-REDC"]}]},{"name":"Alfonso Mart\u00edn Escudero Foundation","award":["PID2019-110751RB-I00"],"award-info":[{"award-number":["PID2019-110751RB-I00"]}]},{"name":"Alfonso Mart\u00edn Escudero Foundation","award":["RED2018-102331-T"],"award-info":[{"award-number":["RED2018-102331-T"]}]},{"name":"Alfonso Mart\u00edn Escudero Foundation","award":["CEX2019-000919-M"],"award-info":[{"award-number":["CEX2019-000919-M"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Chagas disease (CD) is a tropical and potentially fatal infection caused by Trypanosoma cruzi. Although CD was limited to Latin America as a silent disease, CD has become widespread as a result of globalization. Currently, 6\u20138 million people are infected worldwide, and no effective treatment is available. Here, we identify new effective agents against T. cruzi. In short, 16 aryl polyamines were screened in vitro against different T. cruzi strains, and lead compounds were evaluated in vivo after oral administration in both the acute and chronic infections. The mode of action was also evaluated at the energetic level, and its high activity profile could be ascribed to a mitochondria-dependent bioenergetic collapse and redox stress by inhibition of the Fe-SOD enzyme. We present compound 15 as a potential compound that provides a step forward for the development of new agents to combat CD.<\/jats:p>","DOI":"10.3390\/pharmaceutics15010140","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T02:23:06Z","timestamp":1672626186000},"page":"140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of Aryl Polyamines Derivatives as Anti-Trypanosoma cruzi Agents Targeting Iron Superoxide Dismutase"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6262-9344","authenticated-orcid":false,"given":"Rub\u00e9n","family":"Mart\u00edn-Escolano","sequence":"first","affiliation":[{"name":"Laboratory of Molecular & Evolutionary Parasitology, RAPID Group, School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Molina-Carre\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Parasitology, University of Granada, Severo Ochoa s\/n, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Mart\u00edn-Escolano","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Roc\u00edo\/CSIC\/University of Seville, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00aa Paz","family":"Clares","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia Molecular (ICMol), Departamento de Qu\u00edmica Inorg\u00e1nica, Universidad de Valencia, 46980 Paterna, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1365-1323","authenticated-orcid":false,"given":"Cristina","family":"Galiana-Rosell\u00f3","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia Molecular (ICMol), Departamento de Qu\u00edmica Inorg\u00e1nica, Universidad de Valencia, 46980 Paterna, Spain"},{"name":"Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, C\/Ram\u00f3n y Cajal, s\/n, 46115 Alfara del Patriarca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8994-1779","authenticated-orcid":false,"given":"Jorge","family":"Gonz\u00e1lez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia Molecular (ICMol), Departamento de Qu\u00edmica Inorg\u00e1nica, Universidad de Valencia, 46980 Paterna, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Cirauqui","sequence":"additional","affiliation":[{"name":"EMBL Grenoble, 71 Avenue des Martyrs, 38000 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 M.","family":"Llinares","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia Molecular (ICMol), Departamento de Qu\u00edmica Inorg\u00e1nica, Universidad de Valencia, 46980 Paterna, Spain"},{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Universidad de Valencia, C\/Dr. Moliner s\/n, 46100 Burjassot, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Rosales","sequence":"additional","affiliation":[{"name":"Department of Parasitology, University of Granada, Severo Ochoa s\/n, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique","family":"Garc\u00eda-Espa\u00f1a","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia Molecular (ICMol), Departamento de Qu\u00edmica Inorg\u00e1nica, Universidad de Valencia, 46980 Paterna, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4316-2742","authenticated-orcid":false,"given":"Clotilde","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"Department of Parasitology, University of Granada, Severo Ochoa s\/n, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,31]]},"reference":[{"key":"ref_1","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_2","unstructured":"WHO (2022, October 02). World Health Organization WHO: Chagas Disease (American Trypanosomiasis). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/chagas-disease-(american-trypanosomiasis)."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1021\/acsinfecdis.0c00353","article-title":"Chagas disease: Current view of an ancient and global chemotherapy challenge","volume":"6","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Requena-M\u00e9ndez, A., Aldasoro, E., de Lazzari, E., Sicuri, E., Brown, M., Moore, D.A., Gascon, J., and Mu\u00f1oz, J. (2015). Prevalence of Chagas Disease in Latin-American Migrants Living in Europe: A Systematic Review and Meta-analysis. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003540"},{"key":"ref_5","unstructured":"World Health Organization (WHO) (2018, May 30). Chagas Disease (American Trypanosomiasis). Available online: http:\/\/www.who.int\/mediacentre\/factsheets\/fs340\/en\/."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3389\/fpubh.2019.00166","article-title":"Chagas disease: From discovery to a worldwide health problem","volume":"7","author":"Lidani","year":"2019","journal-title":"Front. Public Health"},{"key":"ref_7","unstructured":"DNDi\u2014Drugs for Neglected Diseases Initiative (2022, October 02). Diseases & Projects\u2014Chagas Disease. Available online: https:\/\/www.dndi.org\/diseases-projects\/chagas\/."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1177\/1087057114550585","article-title":"Chagas Disease Drug Discovery: Toward a New Era","volume":"20","author":"Chatelain","year":"2014","journal-title":"J. Biomol. Screen."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1056\/NEJMra1410150","article-title":"Chagas\u2019 Disease","volume":"373","author":"Bern","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1093\/jac\/dkx516","article-title":"What to expect and when: Benznidazole toxicity in chronic Chagas\u2019 disease treatment","volume":"73","author":"Aldasoro","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1093\/infdis\/jis331","article-title":"Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population","volume":"206","author":"Mejia","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"65108","DOI":"10.1039\/C4RA09866H","article-title":"Synthetic single and double aza-scorpiand macrocycles act as inhibitors of the antioxidant enzymes iron superoxide dismutase and trypanothione reductase in Trypanosoma cruzi with promising results in a murine model","volume":"4","author":"Olmo","year":"2014","journal-title":"RSC Adv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1021\/acs.jmedchem.9b01554","article-title":"Toward a Rational Design of Polyamine-Based Zinc-Chelating Agents for Cancer Therapies","volume":"63","author":"Villalonga","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1590\/S0074-02762010000200022","article-title":"In vitro and in vivo experimental models for drug screening and development for Chagas disease","volume":"105","author":"Romanha","year":"2010","journal-title":"Mem. Do Inst. Oswaldo Cruz"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Nwaka, S., Besson, D., Ramirez, B., Maes, L., Matheeussen, A., Bickle, Q., Mansour, N.R., Yousif, F., Townson, S., and Gokool, S. (2011). Integrated Dataset of Screening Hits against Multiple Neglected Disease Pathogens. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001412"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1017\/S003118201300142X","article-title":"Screening strategies to identify new chemical diversity for drug development to treat kinetoplastid infections","volume":"141","author":"Don","year":"2014","journal-title":"Parasitology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/nrd4683","article-title":"Hit and lead criteria in drug discovery for infectious diseases of the developing world","volume":"14","author":"Katsuno","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1080\/17460441.2018.1417380","article-title":"Phenotypic screening approaches for Chagas disease drug discovery","volume":"13","author":"Chatelain","year":"2018","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1246\/bcsj.71.717","article-title":"The Reaction of Phthalic Anhydride with Diethylenetriamine and Triethylenetetramine. A Literature Correction","volume":"71","author":"Onopchenko","year":"1998","journal-title":"Bull. Chem. Soc. Jpn."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4301","DOI":"10.1002\/ejic.200500403","article-title":"A New Zn II Tweezer Pyridine-Naphthalene System\u2014An Off-On-Off System Working in a Biological pH Window","volume":"2005","author":"Aucejo","year":"2005","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6173","DOI":"10.1021\/ic7023956","article-title":"Anion Detection by Fluorescent Zn (II) Complexes of Functionalized Polyamine Ligands","volume":"47","author":"Lima","year":"2008","journal-title":"Inorg. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/j.ica.2006.11.006","article-title":"Synthesis and photophysical properties of dansyl-based polyamine ligands and their Zn (II) complexes","volume":"360","author":"Parola","year":"2007","journal-title":"Inorg. Chim. Acta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1021\/ic5029004","article-title":"Equilibrium, Kinetic, and Computational Studies on the Formation of Cu2+ and Zn2+ Complexes with an Indazole-Containing Azamacrocyclic Scorpiand: Evidence for Metal-Induced Tautomerism","volume":"54","author":"Verdejo","year":"2015","journal-title":"Inorg. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1039\/b927418a","article-title":"Tritopic phenanthroline and pyridine tail-tied aza-scorpiands\u2020","volume":"8","author":"Llinares","year":"2010","journal-title":"Org. Biomol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5643","DOI":"10.1021\/acs.jmedchem.8b00468","article-title":"Second Generation of Mannich Base-Type Derivatives with in Vivo Activity against Trypanosoma cruzi","volume":"61","author":"Paucar","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.actatropica.2008.08.006","article-title":"Biological characterization of Trypanosoma cruzi stocks 658 from domestic and sylvatic vectors in Sierra Nevada of Santa Marta, Colombia","volume":"108","year":"2008","journal-title":"Acta Trop."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1002\/j.1460-2075.1990.tb07462.x","article-title":"Trypanosoma cruzi glycosomal glyceralde-661 hyde-3-phosphate dehydrogenase does not conform to the \u2018hotspot\u2019 topogenic signal model","volume":"9","author":"Kendall","year":"1990","journal-title":"EMBO J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ejmech.2018.12.034","article-title":"New polyamine drugs as more effective antichagas agents than benznidazole in both the acute and chronic phases","volume":"164","author":"Clares","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.bmc.2019.01.033","article-title":"Synthesis and biological evaluation of new long-chain squaramides as anti-chagasic agents in the BALB\/c mouse model","volume":"27","author":"Vega","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4653","DOI":"10.1128\/AAC.00520-15","article-title":"Limited Ability of Posaconazole To Cure both Acute and Chronic Trypanosoma cruzi Infections Revealed by Highly Sensitive In Vivo Imaging","volume":"59","author":"Francisco","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1084\/jem.20071393","article-title":"Divergent roles of endothelial NF-\u03baB in multiple organ injury and bacterial clearance in mouse models of sepsis","volume":"205","author":"Ye","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/j.1550-7408.1997.tb05734.x","article-title":"Comparative Aspects of Energy Metabolism in Plant Trypanosomatids","volume":"44","author":"Osuna","year":"1997","journal-title":"J. Eukaryot. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1002\/cmdc.201800512","article-title":"Synthesis and Biological in vitro and in vivo Evaluation of 2-(5-Nitroindazol-1-yl)ethylamines and Related Compounds as Potential Therapeutic Alternatives for Chagas Disease","volume":"13","year":"2018","journal-title":"ChemMedChem"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sandes, J.M., Fontes, A., Regis-da-Silva, C.G., Brelaz De Castro, M.C.A., Lima-Junior, C.G., Silva, F.P.L., Vasconcellos, M.L.A.A., and Figueiredo, R.C.B.Q. (2014). Trypanosoma cruzi Cell Death Induced by the Morita-Baylis-Hillman Adduct 3-Hydroxy-2-Methylene-3-(4-Nitrophenylpropanenitrile). PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093936"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e02288-16","DOI":"10.1128\/AAC.02288-16","article-title":"Enterocin AS-48 as evidence for the use of bacteriocins as new leishmanicidal agents","volume":"61","author":"Saugar","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","first-page":"914129","article-title":"Trypanosoma cruzi: Seroprevalence Detection in Suburban Population of Santiago de Quer\u00e9taro (Mexico)","volume":"2012","year":"2011","journal-title":"Sci. World J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/0003-2697(87)90489-1","article-title":"Assaying for Superoxide Dismutase Activity: Some Large Consequences of Minor Changes in Conditions","volume":"161","author":"Beyer","year":"1987","journal-title":"Anal. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1021\/acsinfecdis.2c00123","article-title":"An Updated View of the Trypanosoma cruzi Life Cycle: Intervention Points for an E ff ective Treatment","volume":"8","author":"Rosales","year":"2022","journal-title":"ACS Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1021\/acsinfecdis.8b00298","article-title":"Drug Discovery for Kinetoplastid Diseases: Future Directions","volume":"5","author":"Rao","year":"2019","journal-title":"ACS Infect. Dis."},{"key":"ref_41","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_42","doi-asserted-by":"crossref","unstructured":"Porr\u00e1s, A.I., Yadon, Z.E., Altcheh, J., Britto, C., Chaves, G.C., Flevaud, L., Martins-Filho, O.A., Ribeiro, I., Schijman, A.G., and Shikanai-Yasuda, M.A. (2015). Target Product Profile (TPP) for Chagas Disease Point-of-Care Diagnosis and Assessment of Response to Treatment. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003697"},{"key":"ref_43","unstructured":"(2022, October 28). DNDi Chagas Disease Target Product Profile. Available online: https:\/\/www.dndi.org\/diseases-projects\/chagas\/chagas-target-product-profile\/)."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4807","DOI":"10.2147\/DDDT.S90208","article-title":"Translational challenges of animal models in Chagas disease drug development: A review","volume":"9","author":"Chatelain","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Canavaci, A.M.C., Bustamante, J.M., Padilla, A.M., Brandan, C.M.P., Laura, 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_46","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_47","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.actatropica.2009.10.007","article-title":"Benznidazole alters the pattern of Cyclophosphamide-induced reactivation in experimental Trypanosoma cruzi-dependent lineage infection","volume":"113","author":"Santos","year":"2010","journal-title":"Acta Trop."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1093\/jac\/dkaa030","article-title":"Assessing the effectiveness of AS-48 in experimental mice models of Chagas\u2019 disease","volume":"75","author":"Maqueda","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1093\/infdis\/jit420","article-title":"New, Combined, and Reduced Dosing Treatment Protocols Cure Trypanosoma cruzi Infection in Mice","volume":"209","author":"Bustamante","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1006\/scdb.2001.0282","article-title":"Reactive oxygen species and mitochondrial diseases","volume":"12","author":"Kirkinezos","year":"2001","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.bbamcr.2006.08.019","article-title":"Metabolic functions of glycosomes in trypanosomatids","volume":"1763","author":"Michels","year":"2006","journal-title":"Biochim. Biophys. Acta\u2014Mol. Cell Res."},{"key":"ref_52","first-page":"1066","article-title":"Trypanothione Reductase and Superoxide Dismutase as Current Drug Targets for Trypanosoma cruzi: An Overview of Compounds with Activity against Chagas Disease","volume":"24","author":"Galiano","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_53","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":"56","author":"Hall","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_54","first-page":"1","article-title":"Insights into Chagas treatment based on the potential of bacteriocin AS-48","volume":"10","author":"Rosales","year":"2019","journal-title":"IJP Drugs Drug Resist."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.jacc.2016.12.023","article-title":"Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial","volume":"69","author":"Morillo","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"287","DOI":"10.2174\/1381612023396177","article-title":"Chemotherapy of Chagas disease","volume":"8","author":"Urbina","year":"2002","journal-title":"Curr. Pharm. Des."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e02410-16","DOI":"10.1128\/AAC.02410-16","article-title":"Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice","volume":"61","author":"Perin","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ijpddr.2019.11.004","article-title":"Current trends in the pharmacological management of Chagas disease","volume":"12","author":"Ribeiro","year":"2020","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/j.drudis.2016.06.021","article-title":"Drug repositioning approaches to parasitic diseases: A medicinal chemistry perspective","volume":"21","author":"Ferreira","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e34039","DOI":"10.7554\/eLife.34039","article-title":"Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure","volume":"7","author":"Padilla","year":"2018","journal-title":"eLife"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.ijpddr.2016.08.003","article-title":"Assessing anti-T. cruzi candidates in vitro for sterile cidality","volume":"6","author":"Cal","year":"2016","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1517\/17460441.2013.845554","article-title":"Design or screening of drugs for the treatment of Chagas disease: What shows the most promise?","volume":"8","author":"Lepesheva","year":"2013","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1097\/QCO.0000000000000192","article-title":"The use of posaconazole against Chagas disease","volume":"28","author":"Molina","year":"2015","journal-title":"Curr. Opin. Infect. Dis."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/1\/140\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:49:03Z","timestamp":1760147343000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/1\/140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,31]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["pharmaceutics15010140"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15010140","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,31]]}}}