Phomaligols F-I, polyoxygenated cyclohexenone derivatives from marine-derived fungus Aspergillus flavus BB1

By tracing the ¹³C NMR resonances for carbonyls and enols, four new oxidized phomaligol derivatives, phomaligols F-I (1-4), along with seven known compounds (5-11) were isolated from the culture of the fungus Aspergillus flavus BB1 isolated from the marine shellfish Meretrix meretrix collected on Hailing Island, Yangjiang, China. The chemical structures and the absolute configurations of the new compounds were elucidated by MS, NMR, ECD, optical rotation, and ¹³C NMR calculations. Compounds 1 and 2 represent the first examples of phomaligol derivatives that contain an unusual bicyclic skeleton. All isolated compounds were tested for their cytotoxic activity. Among them, sporogen-AO 1 (8) showed potent inhibitory activity against the cancer cell lines A549, H1299, SK-BR-3, and HCT116 with IC₅₀ values of 0.13, 0.78, 1.19, and 1.32 μM, respectively. Phomaligol G (2) displayed cytotoxic activity against the A549 and H1299 cell lines with IC₅₀ values of 46.86 and 51.87 μM respectively. Additionally, phomaligol H (3) demonstrated cytotoxic activity against the A549 cell line with an IC₅₀ value of 65.53 μM. Mechanistic studies of compound 8 showed that it induced apoptosis of HCT116 cells in a dose-dependent manner.