Aromatic polyketides from the marine-derived fungus Aspergillus unguis PM03: α-glucosidase inhibitory activity, structure-activity relationship, molecular docking and ADMET evaluation

Chemical investigation of Aspergillus unguis PM03 yielded eight known aromatic polyketides, including unguinol (1), nidulin (2), 2,4-dichlorounguinol (3), 2-chlorounguinol (4), emeguisin B (5), aspergillusether A (6), guisinol (7), and isosclerone (8). Their structures were established by spectroscopic analysis and comparison with published data. All isolated compounds were evaluated for cytotoxicity against four human cancer cell lines (KB, Hep-G2, A549, and MCF-7) and for α-glucosidase inhibitory activity. None of the compounds exhibited significant cytotoxicity (IC50 > 128 μM). Compounds 1, 3, 5, 7, and 8 inhibited α-glucosidase, with guisinol (7) showing the strongest activity (IC50 = 4.01 μM), followed by isosclerone (8) (11.39 μM), emeguisin B (5) (24.31 μM), unguinol (1) (26.28 μM), and 2,4-dichlorounguinol (3) (28.83 μM). To our knowledge, this is the first report of the α-glucosidase inhibitory activity of compounds 1–7. A preliminary structure–activity relationship analysis suggested that the substitution pattern of the aromatic polyketides may affect their inhibitory activity. Molecular docking of compounds 1–7 and four aromatic polyketides previously isolated in our studies was performed against penicillin-binding protein 2a (PBP2a; PDB ID: 1MWT), together with in silico ADMET prediction to assess their pharmacokinetic properties.