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Novel mercapto conjugates of oleanolic acid as potential antifungal agents.

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Τίτλος: Novel mercapto conjugates of oleanolic acid as potential antifungal agents.
Συγγραφείς: Sofi ZI; Bioorganic Chemistry Division, CSIR Indian Institute of Integrative Medicine, Srinagar, J&K, 190005, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India., Kantroo HA; Clinical Microbiology and PK-PD Division, CSIR Indian Institute of Integrative Medicine, Srinagar, J&K, 190005, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India., Wani ZA; Clinical Microbiology and PK-PD Division, CSIR Indian Institute of Integrative Medicine, Srinagar, J&K, 190005, India., Shah MU; Bioorganic Chemistry Division, CSIR Indian Institute of Integrative Medicine, Srinagar, J&K, 190005, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India., Bhat KA; Bioorganic Chemistry Division, CSIR Indian Institute of Integrative Medicine, Srinagar, J&K, 190005, India. kabhat@iiim.res.in.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India. kabhat@iiim.res.in., Ahmad Z; Clinical Microbiology and PK-PD Division, CSIR Indian Institute of Integrative Medicine, Srinagar, J&K, 190005, India. zap@iiim.res.in.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India. zap@iiim.res.in.
Πηγή: Archives of microbiology [Arch Microbiol] 2026 Jul 11; Vol. 208 (10). Date of Electronic Publication: 2026 Jul 11.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 0410427 Publication Model: Electronic Cited Medium: Internet ISSN: 1432-072X (Electronic) Linking ISSN: 03028933 NLM ISO Abbreviation: Arch Microbiol Subsets: MEDLINE
Imprint Name(s): Original Publication: Berlin, New York, Springer-Verlag.
Ιατρικοί όροι (MeSH): Antifungal Agents*/pharmacology , Antifungal Agents*/chemistry , Candida albicans*/drug effects , Candida albicans*/growth & development , Oleanolic Acid*/pharmacology , Oleanolic Acid*/chemistry , Oleanolic Acid*/analogs & derivatives , Sulfhydryl Compounds*/chemistry , Sulfhydryl Compounds*/pharmacology, Biofilms/drug effects ; Biofilms/growth & development ; Hyphae/drug effects ; Hyphae/growth & development ; Ergosterol/metabolism ; Virulence/drug effects ; Microbial Sensitivity Tests ; Molecular Docking Simulation ; Animals ; Humans
Περίληψη: The increasing incidence of antifungal resistance in Candida species underscores the urgent need for new agents that effectively inhibit fungal growth and virulence while exhibiting minimal host toxicity. In this study, DBE-7 was identified as a potent antifungal compound with strong activity against Candida albicans. DBE-7 inhibited fungal growth at low micromolar concentrations (MIC = 3.37 µM) and exhibited fungicidal rather than fungistatic activity. The compound markedly impaired key virulence attributes, including hyphal morphogenesis and biofilm formation. Quantitative image analysis demonstrated a concentration-dependent reduction in hyphal elongation and filamentous cell formation, with inhibitory effects comparable to those of fluconazole. DBE-7 also significantly reduced biofilm biomass, indicating its ability to disrupt biofilm architecture. DBE-7 effectively eradicated preformed mature biofilms in a concentration-dependent manner, indicating its ability not only to prevent biofilm development but also to disrupt established biofilm. Kill kinetics revealed rapid and sustained fungicidal activity in a time- and concentration-dependent manner. DBE-7 also displayed low cytotoxicity toward mammalian cell lines, maintaining high cell viability within its antifungal concentration range. Molecular docking revealed a strong binding affinity of DBE-7 toward lanosterol 14-α-demethylase (LDM), while the marked reduction in cellular ergosterol levels in DBE-7-treated C. albicans further supports disruption of the ergosterol biosynthetic pathway, suggesting potential targeting of LDM. Collectively, these findings highlight DBE-7 as a promising antifungal candidate that effectively targets C. albicans growth and virulence while exhibiting a favorable safety profile, supporting its further preclinical development.
(© 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Competing Interests: Declarations. Conflicts of 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.
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Grant Information: GAP-3103 Department of Biotechnology, Ministry of Science and Technology, India; GAP-2191 Department of Science and Technology, Ministry of Science and Technology, India
Contributed Indexing: Keywords: Candida albicans; Antifungal drug discovery; Biofilm inhibition; Ergosterol inhibition; Hyphal inhibition; Molecular docking; Synergism
Substance Nomenclature: 0 (Antifungal Agents)
6SMK8R7TGJ (Oleanolic Acid)
Z30RAY509F (Ergosterol)
0 (Sulfhydryl Compounds)
Entry Date(s): Date Created: 20260711 Date Completed: 20260711 Latest Revision: 20260711
Update Code: 20260712
DOI: 10.1007/s00203-026-04952-0
PMID: 42435079
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1432-072X
DOI:10.1007/s00203-026-04952-0