Bioactive Polyketides From the Mangrove Endophytic Fungus Cytospora Rhizophorae SCNU-F0054

Mangrove endophytic fungi are recognized as a prolific source of structurally unique and bioactive secondary metabolites. In this study, we aimed to investigate the chemical diversity and biological potential of the mangrove-derived fungus Cytospora rhizophorae SCNU-F0054, leading to the isolation of four new polyketides, namely (14R, 15'R)-integracin D (1), cytospyrone B (8), furanone 2 (12), 4-ethyl-2-hydroxy-2,5-dimethylcyclopent-4-ene-1,3-dione (14), together with ten known analogues. Their structures were elucidated based on extensive spectroscopic analyses, TDDFT-ECD calculations, and comparisons of experimental ECD spectra. In antibacterial assays, compound 7 exhibited potent, broad-spectrum activity against all tested strains, with MIC ranging from 1.56 to 6.25 µg/mL. Among the dimeric alkylresorcinols, the sulfated derivative 1 was most active against S. aureus and E. coli. In α-glucosidase inhibitory assay, alkylresorcinols 1, 2, 4, and 5 outperformed the positive control (1-deoxynojirimycin), with IC₅₀ values of 3.53-12.35 µM. Overall, the alkylresorcinol subclass demonstrated stronger antibacterial and enzyme inhibitory activities than the other polyketides in this study, highlighting their potential as promising lead compounds for further pharmaceutical development.