{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:04:04Z","timestamp":1791234244916,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["301881\/2025-1"],"award-info":[{"award-number":["301881\/2025-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004586","name":"FAPERJ","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004901","name":"FAPEMIG","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"crossref"}]},{"name":"FIOCRUZ"},{"name":"\u201cCoordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior do Brasil\u201d","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Royal Society International Science Partnerships Fund","award":["ICAO\/R1\/231073"],"award-info":[{"award-number":["ICAO\/R1\/231073"]}]},{"name":"Royal Society for a University Research Fellowship and Enhancement"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Chagas disease is caused by the protozoan Trypanosoma cruzi, and its current treatment is limited to the use of two nitroderivatives, benznidazole (Bz) and nifurtimox; however, their toxicity often leads to discontinuation, justifying the search for new therapeutic options. The biological activity of quinones has long shown efficacy towards pathogenic microorganisms. In our previous investigations, two naphthoquinones combining ortho- and para-quinoidal moieties exhibited remarkable trypanocidal activity and presented low toxicity to host cells. Here, these two active compounds were further assessed. On trypomastigotes and epimastigotes, brominated (NQ1) and chlorinated (NQ2) nor-beta-lapachone-derived 1,2,3-triazoles were more active than Bz, presenting IC50\/24 h values in the range of 0.8 to 3.1 \u00b5M. NQ1-treated epimastigotes showed a mitochondrial impairment and reactive oxygen species (ROS) production under electron microscopy and flow cytometry. The in vitro evaluation of both combinations of compounds with Bz indicated an additive interaction. In vivo, oral treatment with NQ1 reduced parasitemia in an acute model, with no evidence of toxicity. The treatment also led to a reduction in myocarditis, decreasing the PR interval in electrocardiographic analysis and reversing the sinus bradycardia caused by infection. These data suggest that T. cruzi mitochondrion are part of the NQ1 mechanism of action. In vivo, this compound presented moderate trypanocidal and promising anti-inflammatory activity. Its combination with Bz could enhance current therapeutic protocols and should be better explored in the future.<\/jats:p>","DOI":"10.3390\/pathogens15010017","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T10:57:18Z","timestamp":1766487438000},"page":"17","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Trypanocidal Activity of Dual Redox-Active Quinones: Trypanosoma cruzi Mitochondrion as a Target Organelle In Vitro and Anti-Inflammatory Properties In Vivo"],"prefix":"10.3390","volume":"15","author":[{"given":"Raquel B.","family":"Duarte","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor F. S.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana M. C.","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel M.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5469-8860","authenticated-orcid":false,"given":"Emilay B. T.","family":"Diogo","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Exatas, Departamento de Qu\u00edmica, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2896-0487","authenticated-orcid":false,"given":"Renata G.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Exatas, Departamento de Qu\u00edmica, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2019-7421","authenticated-orcid":false,"given":"Alastair J. J.","family":"Lennox","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of Bristol Cantock\u2019s Close, Bristol BS8 1TS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1281-5453","authenticated-orcid":false,"given":"Eufr\u00e2nio N.","family":"da Silva J\u00fanior","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Exatas, Departamento de Qu\u00edmica, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Pedra-Rezende","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1352-0641","authenticated-orcid":false,"given":"Rubem F. 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