{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:08:01Z","timestamp":1790690881553,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fungal pathogens are an escalating global public health concern, particularly in the context of invasive and opportunistic infections. Cryptococcosis, primarily caused by\n                    <jats:italic>Cryptococcus neoformans var. grubii<\/jats:italic>\n                    , can affect multiple organs and often leads to life\u2010threatening meningitis in immunocompromised individuals. Given limited antifungal therapies and emergence of resistance and toxicity\u2010related constraints, the development of novel anti\u2010cryptococcal agents remains an urgent priority. A library of innovative 3\u2010hydroxypyridin\u20104(1\n                    <jats:italic>H<\/jats:italic>\n                    )\u2010one\u2010based hybrids (\n                    <jats:bold>5a\u2013f<\/jats:bold>\n                    ) was synthesized and evaluated for antimicrobial activity against clinically relevant Gram\u2010positive and Gram\u2010negative bacteria, as well as fungal species\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    and\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    var.\n                    <jats:italic>grubbi<\/jats:italic>\n                    . Safety was assessed through cytotoxicity studies in HEK293 and HepG2 cells and hemolytic evaluation, while iron\u2010chelating capacity and lipophilicity were also investigated. All compounds formed stable iron(III) complexes and displayed no significant toxicity up to 25\u2009\u03bcM. Series 1 compounds (\n                    <jats:bold>5a\u2013c<\/jats:bold>\n                    ) were less lipophilic than Series 2 (\n                    <jats:bold>5d\u2013f<\/jats:bold>\n                    ), mainly due to regioisomeric position of hydroxyl group on 2\u2010methyl\u20104\u2010pyridone scaffold, whereas fluorination increased lipophilicity in both series. Notably, compounds\n                    <jats:bold>5c\u2013f<\/jats:bold>\n                    emerged as potent, selective, and nontoxic antifungal agents against\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    var.\n                    <jats:italic>grubii<\/jats:italic>\n                    (MIC\u2009&lt;\u200916\u2009\u00b5g\/mL; CC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009&gt;\u200932\u2009\u00b5g\/mL; HC\n                    <jats:sub>10<\/jats:sub>\n                    \u2009&gt;\u200932\u2009\u00b5g\/mL), highlighting the potential of 3\u2010hydroxypyridin\u20104(1H)\u2010one\u2010based hybrids as a promising approach for cryptococcal meningitis therapy.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70324","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:20:45Z","timestamp":1788445245000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of Novel Ligands for the Treatment of\n                    <i>Cryptococcus neoformans<\/i>\n                    Infection"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4014-2109","authenticated-orcid":false,"given":"Teresa","family":"Rocha","sequence":"first","affiliation":[{"name":"RISE\u2010Health, Departamento de Biomedicina Faculdade de Medicina da Universidade do Porto Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Alves","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica Faculdade de Ci\u00eancias da Universidade do Porto Porto 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Universidade do Porto Porto Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica Faculdade de Ci\u00eancias da Universidade do Porto Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Cagide","sequence":"additional","affiliation":[{"name":"RISE\u2010Health, Departamento de Biomedicina Faculdade de Medicina da Universidade do Porto Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9645-8152","authenticated-orcid":false,"given":"Sofia","family":"Benfeito","sequence":"additional","affiliation":[{"name":"RISE\u2010Health, Departamento de Biomedicina Faculdade de Medicina da Universidade do Porto Porto 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