{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T19:08:22Z","timestamp":1778094502658,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brazilian agencies: Conselho Nacional de Desenvolvimento Cient\u0131fico e Tecnologico","award":["142547\/2018-2"],"award-info":[{"award-number":["142547\/2018-2"]}]},{"name":"Fundac\u00e3o de Amparo \u00e0 Pesquisa no Estado do Rio de Janeiro","award":["260003\/006249\/2024"],"award-info":[{"award-number":["260003\/006249\/2024"]}]},{"name":"Coordenac\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u0131vel Superior","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Vice-Presidente de Pesquisa e Cole\u00e7\u00f5es Biol\u00f3gicas"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives:\u00a0Fonsecaea pedrosoi causes chromoblastomycosis, a neglected chronic subcutaneous mycosis that remains difficult to treat. In this study, we evaluated the toxicity and the antifungal effect of [Ag(1,10-phenanthroline)2]ClO4 (Ag-phen) and [Ag2(3,6,9-trioxaundecanedioate)(1,10-phenanthroline)4]\u00b7EtOH (Ag-tdda-phen) against F. pedrosoi using in silico, in vitro and in vivo approaches. Methods: Pharmacokinetic and toxicological parameters were predicted using ADMETlab 2.0. The toxicity of the complexes was assessed using sheep red blood cells, RAW 264.7 macrophage cells, and larvae of Tenebrio molitor and Galleria mellonella. The effects of these complexes on macrophage adhesion capacity and reactive oxygen species (ROS) production were also investigated using Giemsa staining and dichlorofluorescein diacetate, respectively. In addition, their impact on the survival of G. mellonella larvae infected with conidia was evaluated. Results: Overall, computational analyses predicted favorable tolerability profiles for both complexes. In vitro assays with red blood cells and macrophages demonstrated that they exhibited selectivity indexes &gt;10 against F. pedrosoi. These findings were corroborated by in vivo experiments in which both complexes were injected into insect larvae; the complexes demonstrating good tolerability at concentrations of up to 500 mg\/L. Macrophage infection assays revealed that Ag-tdda-phen and Ag-phen markedly reduced the number of intracellular conidia. These effects appear to be associated with oxidative stress, as macrophage production of ROS significantly increased following treatment with the complexes. Furthermore, Ag-tdda-phen improved the survival of G. mellonella larvae infected with F. pedrosoi, demonstrating a protective effect. Conclusions: Collectively, our findings support the notion that silver(I)-phen derivatives represent promising candidates for the development of therapeutic options against CBM infections caused by F. pedrosoi.<\/jats:p>","DOI":"10.3390\/ph18121819","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T08:49:22Z","timestamp":1764665362000},"page":"1819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Biological Activity of Silver(I)-1,10-Phenanthroline Complexes Against Fonsecaea pedrosoi: In Silico Predictions, In Vitro Macrophage Interactions and In Vivo Efficacy in Galleria mellonella"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4191-790X","authenticated-orcid":false,"given":"Ingrid S.","family":"Sousa","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Taxonomia, Bioqu\u00edmica e Bioprospec\u00e7\u00e3o de Fungos (LTBBF), Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5036-3837","authenticated-orcid":false,"given":"Lucas","family":"Giovanini","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4602-2550","authenticated-orcid":false,"given":"Carolline M. A.","family":"Lorentino","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2126-873X","authenticated-orcid":false,"given":"Iuri C.","family":"Barcellos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malachy","family":"McCann","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Maynooth University, W23 F2H6 Maynooth, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5378-0536","authenticated-orcid":false,"given":"Michael","family":"Devereux","sequence":"additional","affiliation":[{"name":"Center for Biomimetic and Therapeutic Research, Focas Research Institute, Technological University Dublin, D08 CKP1 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0821-8592","authenticated-orcid":false,"given":"Andr\u00e9 L. S.","family":"Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"},{"name":"Rede Micologia RJ, Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3507-4689","authenticated-orcid":false,"given":"Lucimar F.","family":"Kneipp","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Taxonomia, Bioqu\u00edmica e Bioprospec\u00e7\u00e3o de Fungos (LTBBF), Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil"},{"name":"Rede Micologia RJ, Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1128\/CMR.00032-16","article-title":"Chromoblastomycosis","volume":"30","author":"Santos","year":"2017","journal-title":"Clin. 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