{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:47:56Z","timestamp":1790214476834,"version":"4.1.0"},"reference-count":59,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brazilian Agencies: National Council for Scientific and Technological Development"},{"name":"Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State, Brazil","award":["FAPERJ E-26\/211.502\/2021"],"award-info":[{"award-number":["FAPERJ E-26\/211.502\/2021"]}]},{"name":"Coordination of Higher Education Personnel Improvement (CAPES), Brazil","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Rede Micologia RJ"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Sporothrix brasiliensis<\/jats:italic>\n                      is the principal etiological agent responsible for cat-transmitted zoonotic sporotrichosis, which is currently the most prevalent mycosis in South America\u2014especially in Brazil\u2014and is increasingly being reported in other regions. While itraconazole is the standard treatment, its use is limited by hepatotoxicity, high cost, and emerging reports of reduced susceptibility. Complexes of 1,10-phenanthroline-5,6-dione (phendione) with transition metals have previously shown promise as antifungal agents against bacteria, parasites, yeasts and filamentous fungi. This study investigates the\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      antifungal properties of [Cu(phendione)3](ClO4)2.4H2O (Cu-phendione) and [Ag(phendione)2]ClO4 (Ag-phendione) against\n                      <jats:italic>S. brasiliensis<\/jats:italic>\n                      isolates from domestic felines in endemic regions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Six clinical isolates of\n                      <jats:italic>S. brasiliensis<\/jats:italic>\n                      obtained from cutaneous lesions in six felines with laboratory-confirmed sporotrichosis from hyperendemic regions in the state of Rio de Janeiro, Brazil, were investigated. Selection was made according to\n                      <jats:italic>in vitro<\/jats:italic>\n                      Minimum Inhibitory Concentration (MIC) response criteria for itraconazole (\u201cwild type\u201d WT = MIC \u2264 2 \u00b5g\/mL; \u201cnon-wild type\u201d NWT = MIC \u2265 4 \u00b5g\/mL). The American Type Culture Collection (ATCC)\n                      <jats:italic>S. brasiliensis<\/jats:italic>\n                      MYA 4823 was included. The minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of phendione, its metal complexes, and simple silver and copper salts were evaluated against\n                      <jats:italic>S. brasiliensis<\/jats:italic>\n                      saprophytic and parasitic phases. Additionally,\n                      <jats:italic>in vivo<\/jats:italic>\n                      antifungal efficacy was assessed using\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      larvae as a model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both metal complexes exhibited low MIC (0.3\u20135 \u00b5M) and MFC (0.3\u201310 \u00b5M) values against conidia and yeast forms of both WT (\u201csensitive\u201d) and NWT (\u201cresistant\u201d)\n                      <jats:italic>S. brasiliensis<\/jats:italic>\n                      clinical isolates. Notably, MFC values were equal to or at most twice the MICs, indicating a fungicidal profile, even against itraconazole-resistant strains.\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      treated groups exhibited higher values than the\n                      <jats:italic>S. brasiliensis<\/jats:italic>\n                      group (6.0 days) while all compounds provided larvae mean survival higher than the itraconazole treated group (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&gt;\u00a00.05). Cu-phendione was the compound that conferred the highest median survival (8.0 days).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Silver(I) and Copper(II) complexes of 1,10-phenanthroline-5,6-dione demonstrated both inhibitory and fungicidal activity against itraconazole-resistant\n                      <jats:italic>S. brasiliensis<\/jats:italic>\n                      isolates from diseased cats residing in the Brazilian hyperendemic region, highlighting their promise as novel antifungal agents. This finding is notable because drugs currently used for sporotrichosis treatment are characterized as fungistatic. This study provides data on alternative molecules that may be considered for future control of sporotrichosis, a zoonosis currently spreading throughout Latin America.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.21129","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T08:20:26Z","timestamp":1778055626000},"page":"e21129","source":"Crossref","is-referenced-by-count":1,"title":["Silver(I) and Copper(II) complexes of 1,10-phenanthroline-5,6-dion\n                    <i>e<\/i>\n                    inhibit\n                    <i>Sporothrix brasiliensis<\/i>\n                    azole-resistant clinical isolates"],"prefix":"10.7717","volume":"14","author":[{"given":"La\u00eds Cavalcanti dos Santos Velasco","family":"de Souza","sequence":"first","affiliation":[{"name":"Center for Microorganisms\u2019 Investigation, Microbiology and Parasitology Department, Biomedical Institute, Federal Fluminense University, 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Souza","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Taxonomy, Biochemistry and Bioprospecting of Fungi, Oswaldo Cruz Institute, Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Rodrigo Santos","family":"Silva","sequence":"additional","affiliation":[{"name":"Centre for Biological and Health Sciences, Federal Sergipe University, S\u00e3o Crist\u00f3v\u00e3o, Sergipe, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Luiz Dantas","family":"Machado","sequence":"additional","affiliation":[{"name":"Center for Microorganisms\u2019 Investigation, Microbiology and Parasitology Department, Biomedical Institute, Federal Fluminense University, Niter\u00f3i, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor Manuel","family":"Mora-Montes","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda, Divisi\u00f3n de Ciencias Naturales y Exactas, Universidad de Guanajuato,  Guanajuato, Noria Alta, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucimar Ferreira","family":"Kneipp","sequence":"additional","affiliation":[{"name":"Laboratory of Taxonomy, Biochemistry and Bioprospecting of Fungi, Oswaldo Cruz Institute, Rio de Janeiro, Rio de Janeiro, Brazil"},{"name":"Rede Micologia RJ, Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro, Rio de Janeiro,  Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malachy","family":"McCann","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Maynooth University, National University of Ireland, Maynooth, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Devereux","sequence":"additional","affiliation":[{"name":"Center for Biomimetics and Therapeutics Research, Focas Research Institute, University of 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