{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:38:51Z","timestamp":1777610331882,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Programa de Doutorado Sandu\u00edche no Exterior (PDSE)","award":["88881.189584\/2018-01"],"award-info":[{"award-number":["88881.189584\/2018-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hydroxymethylnitrofurazone (NFOH) is a therapeutic candidate for Chagas disease (CD). It has negligible hepatotoxicity in a murine model compared to the front-line drug benznidazole (BZN). Here, using Trypanosoma cruzi strains that express bioluminescent and\/or fluorescent reporter proteins, we further investigated the in vitro and in vivo activity of NFOH to define whether the compound is trypanocidal or trypanostatic. The in vitro activity was assessed by exploiting the fluorescent reporter strain using wash-out assays and real-time microscopy. For animal experimentation, BALB\/c mice were inoculated with the bioluminescent reporter strain and assessed by highly sensitive in vivo and ex vivo imaging. Cyclophosphamide treatment was used to promote parasite relapse in the chronic stage of infection. Our data show that NFOH acts by a trypanostatic mechanism, and that it is more active than BZN in vitro against the infectious trypomastigote form of Trypanosoma cruzi. We also found that it is more effective at curing experimental infections in the chronic stage, compared with the acute stage, a feature that it shares with BZN. Therefore, given its reduced toxicity, enhanced anti-trypomastigote activity, and curative properties, NFOH can be considered as a potential therapeutic option for Chagas disease, perhaps in combination with other trypanocidal agents.<\/jats:p>","DOI":"10.3390\/ijms22136930","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T11:45:40Z","timestamp":1624880740000},"page":"6930","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Image-Based In Vitro Screening Reveals the Trypanostatic Activity of Hydroxymethylnitrofurazone against Trypanosoma cruzi"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2540-6395","authenticated-orcid":false,"given":"Cau\u00ea","family":"Scarim","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Sao Paulo State University (UNESP), Araraquara, Sao Paulo 14800-903, Brazil"},{"name":"Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9314-0026","authenticated-orcid":false,"given":"Francisco","family":"Olmo","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Ferreira","sequence":"additional","affiliation":[{"name":"LAPEN\u2014Laboratory of Design and Synthesis of Chemotherapeutic Agents Potentially Active on Neglected Diseases, Department of Pharmacy, School of Pharmaceutical Sciences, University of Sao Paulo (USP), Sao Paulo 05508-9000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung","family":"Chin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sao Paulo State University (UNESP), Araraquara, Sao Paulo 14800-903, Brazil"},{"name":"Advanced Research Center in Medicine, School of Medicine, Union of the Colleges of the Great Lakes (UNILAGO), S\u00e3o Jos\u00e9 do Rio Preto, Sao Paulo 15030-070, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3475-8130","authenticated-orcid":false,"given":"Amanda","family":"Francisco","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1590\/S0037-86822010000500001","article-title":"Centen\u00e1rio do descobrimento da doen\u00e7a de Chagas: Desafios e perspectivas","volume":"43","author":"Malafaia","year":"2010","journal-title":"Rev. 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