Academic Journal
Antifungal effects of dibenzofuran derivatives against multi-azole resistant Candida albicans.
| Τίτλος: | Antifungal effects of dibenzofuran derivatives against multi-azole resistant Candida albicans. |
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| Συγγραφείς: | Faleye OO; School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea., Mukhles MB; School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea., Boya BR; School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea., Kim YG; School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea., Lee JH; School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea. Electronic address: jinhlee@ynu.ac.kr., Lee J; School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea. Electronic address: jtlee@ynu.ac.kr. |
| Πηγή: | Bioorganic chemistry [Bioorg Chem] 2026 Aug 15; Vol. 178, pp. 109971. Date of Electronic Publication: 2026 May 08. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Original Publication: New York, London, Academic Press. |
| Ιατρικοί όροι (MeSH): | Antifungal Agents*/pharmacology , Antifungal Agents*/chemistry , Antifungal Agents*/chemical synthesis , Candida albicans*/drug effects , Drug Resistance, Fungal*/drug effects , Dibenzofurans*/pharmacology , Dibenzofurans*/chemistry , Dibenzofurans*/chemical synthesis , Benzofurans*/pharmacology , Benzofurans*/chemistry , Benzofurans*/chemical synthesis, Biofilms/drug effects ; Microbial Sensitivity Tests ; Structure-Activity Relationship ; Dose-Response Relationship, Drug ; Humans ; Molecular Structure ; Animals |
| Περίληψη: | The emergence of multi-azole resistant Candida albicans strains poses a major therapeutic challenge, largely due to their biofilm formation and hyphal development. In this study, the antifungal and antivirulence properties of 18 dibenzofuran derivatives were evaluated against a multi-azole resistant C. albicans strain. Dibenzofuran-4‑boronic acid (DBFBA) and dibenzofuran-2-carboxaldehyde (DBFC) emerged as the most active compounds, with DBFBA exhibiting the MIC of 30 μg/mL. Both compounds inhibited 94-98% biofilm at 10 μg/mL, suppressed hyphal morphogenesis and impaired cell aggregation at sub-MICs (5 μg/mL). DBFBA and related boronic acid derivatives further demonstrated potent antifungal activities across clinically relevant Candida strains, such as C. glabrata, C. parapsilosis, and C. auris. Both compounds induced intracellular reactive oxygen species (ROS) and increased cellular ergosterol levels, supporting a mechanism distinct from direct ergosterol inhibition. Serial passage experiment revealed low propensity for resistance development compared with fluconazole. Drug interaction studies revealed synergy with terbinafine for both compounds. DBFBA additionally downregulated the virulence-associated iron acquisition gene RBT5. Importantly, both compounds showed minimal toxicity in HepG2 cells, Caenorhabditis elegans and Raphanus sativus models. In silico ADME analysis further supported both compounds favorable drug-like profile. These findings position dibenzofuran derivatives, particularly DBFBA, as promising antifungal candidates against azole-resistant Candida species. (Copyright © 2024. Published by Elsevier Inc.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Antibiofilm; Antifungal; Candida albicans; Dibenzofuran derivatives; Virulence |
| Substance Nomenclature: | 0 (Antifungal Agents) 8U54U639VI (dibenzofuran) 0 (Dibenzofurans) 0 (Benzofurans) |
| Entry Date(s): | Date Created: 20260514 Date Completed: 20260717 Latest Revision: 20260717 |
| Update Code: | 20260717 |
| DOI: | 10.1016/j.bioorg.2026.109971 |
| PMID: | 42134203 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1090-2120 |
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| DOI: | 10.1016/j.bioorg.2026.109971 |