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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Candida albicans biofilms are a major cause of persistent infections and contribute to antifungal resistance as well as limitations in drug delivery. Targeting virulence traits such as biofilm formation and hyphal transition represents an effective strategy for controlling fungal pathogenicity without exerting strong selective pressure on planktonic growth. In this study, a library of structurally diverse benzophenone derivatives was screened to identify compounds with antibiofilm and anti-hyphal activities against azole-resistant C. albicans. Most benzophenone derivatives exhibited weak antifungal activity (MIC \u2265 200 \u00b5g\/mL). However, several halogenated benzophenones markedly suppressed biofilm formation. Among them, decafluorobenzophenone at 10 \u00b5g\/mL displayed the strongest inhibition, reducing biofilm formation to approximately 1\u20132% of control levels while maintaining substantial planktonic cell viability. Microscopy confirmed hyphal suppression, while qRT-PCR showed a 36-fold reduction in ALS3 expression. These findings indicate that multi-halogenated benzophenones act primarily as anti-virulence agents targeting biofilm formation and hyphal development. Molecular docking suggested a possible interaction of decafluorobenzophenone with the Als3 binding pocket. Decafluorobenzophenone showed low toxicity, with unaffected Caenorhabditis elegans viability at 10 \u00b5g\/mL, plant germination at 100 \u00b5g\/mL, and only slight hemolysis at 100 \u00b5g\/mL. The results highlight halogen substitution as a key structural determinant and identify benzophenone scaffolds as promising leads for developing novel antibiofilm strategies against azole-resistant Candida infections.<\/jats:p>","DOI":"10.3390\/ijms27177528","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:19Z","timestamp":1787572039000},"page":"7528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antibiofilm and Anti-Hyphal Activities of Halogenated Benzophenones Against Azole-Resistant Candida albicans"],"prefix":"10.3390","volume":"27","author":[{"given":"Juyeon","family":"Jo","sequence":"first","affiliation":[{"name":"School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3720-7805","authenticated-orcid":false,"given":"Ziyad","family":"Abdelaal","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8355-760X","authenticated-orcid":false,"given":"Yong-Guy","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Clean Technology, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Hyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Clean Technology, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1383-1682","authenticated-orcid":false,"given":"Jintae","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41579-022-00720-1","article-title":"Tackling the emerging threat of antifungal resistance to human health","volume":"20","author":"Fisher","year":"2022","journal-title":"Nat. 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