{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:34:02Z","timestamp":1760146442484,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T00:00:00Z","timestamp":1730505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER (European Fund for Regional Development)-COMPETEQREN-EU","award":["UIDB\/04050\/2020","UID\/QUI\/00686\/2020","UI\/BD\/150872\/2021","2020.08235.BD","SFRH\/BD\/133513\/2017","COVID\/BD\/152169\/2021"],"award-info":[{"award-number":["UIDB\/04050\/2020","UID\/QUI\/00686\/2020","UI\/BD\/150872\/2021","2020.08235.BD","SFRH\/BD\/133513\/2017","COVID\/BD\/152169\/2021"]}]},{"DOI":"10.13039\/501100001871","name":"Ph.D. scholarships","doi-asserted-by":"publisher","award":["UIDB\/04050\/2020","UID\/QUI\/00686\/2020","UI\/BD\/150872\/2021","2020.08235.BD","SFRH\/BD\/133513\/2017","COVID\/BD\/152169\/2021"],"award-info":[{"award-number":["UIDB\/04050\/2020","UID\/QUI\/00686\/2020","UI\/BD\/150872\/2021","2020.08235.BD","SFRH\/BD\/133513\/2017","COVID\/BD\/152169\/2021"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The rise in non-albicans Candida species, exhibiting unpredictable antifungal resistance, complicates treatment and contributes to the growing threat of invasive, life-threatening infections. This study evaluates the antifungal activity of four benzo[a]phenoxazine derivatives (C34, C35, A42, and A44) against 14 Candida strains following EUCAST standards. Fluconazole interactions are analysed through fractional inhibitory concentration index (FICI) calculation and response surface analysis based on the Bliss model. Macrophage-like J774A.1 cells are used to assess Candida killing in the presence of synergistic compounds. The MIC values against the different strains vary, with C34 showing the strongest activity, followed by C35, while A42 has the highest MIC values, indicating lower efficacy. However, A42 demonstrates the best synergy with fluconazole against fluconazole-resistant Candida strains. Cytotoxicity assays reveal that the chloropropyl group present in C35 and A42 enhances cytocompatibility. Co-culture with macrophages shows significant yeast killing for C. albicans and C. auris when fluconazole and A42 are combined, requiring concentrations 4 and 16 times lower than their MIC values, enhancing antifungal activity. Given fluconazole\u2019s fungistatic nature and the emergence of drug-resistant strains, benzo[a]phenoxazine derivatives\u2019 ability to enhance fluconazole\u2019s efficacy present a promising strategy to address antifungal resistance in critical pathogens. These findings align with global research priorities, offering new potential avenues for developing more effective antifungal therapies.<\/jats:p>","DOI":"10.3390\/molecules29215197","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T09:52:54Z","timestamp":1730713974000},"page":"5197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combining Fluconazole with Benzo[a]phenoxazine Derivatives as a Promising Strategy Against Fluconazole-Resistant Candida Species"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7416-6965","authenticated-orcid":false,"given":"Maria In\u00eas","family":"Pacheco","sequence":"first","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"Centre of Chemistry (CQUM), Department of Chemistry, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"given":"B\u00e1rbara","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Centre of Chemistry (CQUM), Department of Chemistry, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Patr\u00edcia","family":"Pereira-Silva","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"Institute of Science and Innovation for Bio Sustainability (IBS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5468-8491","authenticated-orcid":false,"given":"Augusto","family":"Costa-Barbosa","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"Institute of Science and Innovation for Bio Sustainability (IBS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2048-1190","authenticated-orcid":false,"given":"M. Sameiro T.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Centre of Chemistry (CQUM), Department of Chemistry, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9424-4150","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Sousa","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"Institute of Science and Innovation for Bio Sustainability (IBS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1415-4428","authenticated-orcid":false,"given":"Paula","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"Institute of Science and Innovation for Bio Sustainability (IBS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chow, E.W.L., Pang, L.M., and Wang, Y. 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