{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T06:19:15Z","timestamp":1764656355973,"version":"3.46.0"},"reference-count":150,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["260003\/001221\/2023"],"award-info":[{"award-number":["260003\/001221\/2023"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Programa Inova Fiocruz, and the Instituto Oswaldo Cruz","award":["IOC-008-FIO-22-2-51"],"award-info":[{"award-number":["IOC-008-FIO-22-2-51"]}]},{"name":"Doctoral scholarships","award":["142350\/2020-6"],"award-info":[{"award-number":["142350\/2020-6"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico\u2014CAPES"},{"name":"Postdoctorial scholarships","award":["153198\/2024-9","E-26\/200.400\/2024"],"award-info":[{"award-number":["153198\/2024-9","E-26\/200.400\/2024"]}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["312170\/2023-8","310887\/2023-2","313188\/2021-1","314717\/2020-0"],"award-info":[{"award-number":["312170\/2023-8","310887\/2023-2","313188\/2021-1","314717\/2020-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CNE\/FAPERJ","award":["E26\/203.969\/2024","E26\/201.158\/2022","E26\/204.392\/2024"],"award-info":[{"award-number":["E26\/203.969\/2024","E26\/201.158\/2022","E26\/204.392\/2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Chemotherapy for cutaneous leishmaniasis is hindered by high toxicity, adverse effects, and increasing drug resistance. Thus, safer and more selective therapies are urgently required. Here, we evaluated the antiparasitic efficacy of methylene blue (MB) and new MB, as well as novel ruthenium complex derivatives (NMB-B and NMB-P) against promastigote and amastigote forms of Leishmania amazonensis. Their cytotoxicity and selectivity on L929, HepG2, VERO, J774.G8 cells, and murine peritoneal macrophages were measured. Mechanisms of action were explored via flow cytometry, assessing morphological changes, mitochondrial depolarization, ROS production, and cell death. The compounds inhibited parasite proliferation in a dose and time-dependent manner, achieving submicromolar efficacy against amastigotes (NMB-P = 0.46 \u03bcM). No cytotoxicity was observed on L929, J774.G8, and VERO cells (except NMB), while HepG2 and murine peritoneal macrophages showed low to moderate toxicity. Selective indexes reached 84 for promastigotes and over 500 for amastigotes. The compounds induced mitochondrial depolarization by up to 61% and a five-fold increase in ROS levels, leading to structural damage and parasite death via late apoptosis\/necrosis-like mechanisms. These findings indicate that the compounds act selectively and trigger the release of oxidative species, exerting leishmanicidal activity and warranting further investigation.<\/jats:p>","DOI":"10.3390\/biology14121709","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T13:03:02Z","timestamp":1764594182000},"page":"1709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From Dyes to Drugs? Selective Leishmanicidal Efficacy of Repositioned Methylene Blue and Its Derivatives in In Vitro Evaluation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9201-7584","authenticated-orcid":false,"given":"Deyvison Rhuan","family":"Vasco-dos-Santos","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Inova\u00e7\u00e3o em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz (LITEB\u2014IOC), Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3922-3514","authenticated-orcid":false,"given":"Juliana","family":"Almeida-Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Inova\u00e7\u00e3o em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz (LITEB\u2014IOC), Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6707-8556","authenticated-orcid":false,"given":"Ludmila Ferreira de Almeida","family":"Fiuza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz (LBC\u2014IOC), Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5682-1331","authenticated-orcid":false,"given":"Natalia","family":"Vacani-Martins","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Inova\u00e7\u00e3o em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz (LITEB\u2014IOC), Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z\u00eanis Novais da","family":"Rocha","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica, Universidade Federal da Bahia (UFBA), <i>Campus<\/i> Universit\u00e1rio de Ondina, Salvador 40170-290, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria de Nazar\u00e9 Correia","family":"Soeiro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz (LBC\u2014IOC), Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9136-240X","authenticated-orcid":false,"given":"Andrea","family":"Henriques-Pons","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Inova\u00e7\u00e3o em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz (LITEB\u2014IOC), Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2240-4519","authenticated-orcid":false,"given":"Eduardo Caio","family":"Torres-Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Tripanossomat\u00eddeos, Instituto Oswaldo Cruz (LBqT\u2014IOC), Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9241-2261","authenticated-orcid":false,"given":"Marcos Andr\u00e9","family":"Vannier-Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Inova\u00e7\u00e3o em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz (LITEB\u2014IOC), Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s40249-024-01260-x","article-title":"Prevalence and Attributable Health Burdens of Vector-Borne Parasitic Infectious Diseases of Poverty, 1990\u20132021: Findings from the Global Burden of Disease Study 2021","volume":"13","author":"Zhu","year":"2024","journal-title":"Infect. 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