Purification and characterization of a dihydroxy Oxocyclohexyl acetate derivative from endophytic Aspergillus...

Endophytic fungi are important sources of structurally diverse natural products with potential antifungal activity. In this study, four endophytic fungi were isolated from Rosmarinus officinalis and screened for bioactivity. An isolate identified as Aspergillus candidus was selected based on its antifungal profile, and its secondary metabolites were investigated. Cultivation in modified Czapek Yeast Broth followed by silica gel chromatography yielded a single major metabolite. Comprehensive GC-MS, FTIR, and 1D/2D NMR analysis established its structure as (2E, 7E)-6, 9-dihydroxy-10-(3-hydroxy-5-oxocyclohexyl) deca-2, 7-dien-1-yl acetate (C₁₈H₂₈O₆, 340 Da), which, to the best of our knowledge, has not been previously reported in major chemical databases. Molecular docking and molecular dynamics simulations indicated a stable and plausible binding mode of this metabolite within the active site of Candida albicans lanosterol 14α-demethylase (CYP51), with docking validated using posaconazole as a reference inhibitor. In vitro antifungal testing by agar tube dilution showed modest but reproducible inhibition of C. albicans growth (15.5% and 24.3% inhibition at 500 and 1000 µg/mL, respectively, vs. fluconazole control). Taken together, these findings identify a previously unreported A. candidus metabolite with confirmed antifungal activity and a mechanistically plausible interaction with CYP51, supporting its consideration as a scaffold for further optimization and detailed pharmacological evaluation rather than as a direct clinical candidate at this stage.