{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:47:59Z","timestamp":1790214479797,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"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":"crossref","id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"crossref","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Leishmaniasis is a severe parasitic disease transmitted by sandflies that affects both humans and animals, with clinical manifestations ranging from cutaneous lesions to life-threatening visceral involvement. Current treatments are limited by toxicity, high cost, and the emergence of drug-resistant strains, underscoring the need for safer and more effective therapeutic strategies. In this study, we investigated the antiparasitic potential of combining Amphotericin B, a drug commonly used for leishmaniasis treatment, with 1,10-phenanthroline-5,6-dione (phendione) coordinated to copper (Cu2+-phendione), an experimental coordination compound, against Leishmania amazonensis promastigotes. The combination markedly impaired parasite proliferation, disrupted ultrastructural integrity, and interfered with metabolic activity. Mechanistic analyses revealed the presence of autophagosomes and pronounced mitochondrial alterations in treated parasites, suggesting the induction of cellular stress and the disruption of essential survival pathways. In addition, the treatment reduced the association index with THP-1 cells, indicating a decrease in parasite infectivity. Collectively, these findings demonstrate that the combination of Cu2+-phendione and Amphotericin B exerts potent antiparasitic effects through multiple mechanisms. Our results also showed that Cu2+-phendione combined with AmB displayed an additive effect, although the isobologram suggested that certain ratios approached synergy. The results support the potential of this combination as a novel chemotherapeutic approach against leishmaniasis and provide a basis for future in vivo studies to evaluate safety, efficacy, and optimal dosing strategies.<\/jats:p>","DOI":"10.3390\/tropicalmed11010004","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T11:22:14Z","timestamp":1766575334000},"page":"4","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Vitro Assessment of the Combined Activity of Amphotericin B and Cu2+-1,10-Phenanthroline-5,6-dione Coordination Compound Against Leishmania amazonensis Promastigotes"],"prefix":"10.3390","volume":"11","author":[{"given":"Simone Santiago Carvalho","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora Duarte","family":"Batista","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Devereux","sequence":"additional","affiliation":[{"name":"The Centre for Biomimetic & Therapeutic Research, Focas Research Institute, Technological University Dublin, D08 CKP1 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malachy","family":"McCann","sequence":"additional","affiliation":[{"name":"Chemistry Department, Maynooth University, W23 F2H6 Maynooth, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Departamento de Quimica, Universidade Federal Santa Catarina (UFSC), Florian\u00f3polis 88035-972, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0821-8592","authenticated-orcid":false,"given":"Andr\u00e9 Luis Souza","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Bioqu\u00edmica, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-909, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-8148","authenticated-orcid":false,"given":"Marta Helena","family":"Branquinha","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12982-017-0065-3","article-title":"Challenges in modeling complexity of neglected tropical diseases: A review of dynamics of visceral leishmaniasis in resource limited settings","volume":"14","author":"DebRoy","year":"2017","journal-title":"Emerg. 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