Nigenolides A-H, 13 new microperfuranones with ferroptosis inhibitory activity from the deep-sea-derived Aspergillus...

Thirteen new microperfuranones, including five pairs of enantiomers, (±)-nigenolides A-E (1a/1b-5a/5b), and three racemate nigenolides F-H (6-8), together with four known analogues (9-12) were isolated from a deep-sea-derived Aspergillus niger 3A00562. The absolute configurations of the five pairs of enantiomers were determined by the comparison of the calculated and experimental ECD spectra. Compounds 3a, 4a, 4b, and 12 were able to inhibit RSL3-induced ferroptosis. Compound 12 inhibited ferroptosis of A375 cells and 786-O cells with EC₅₀ values of 0.76 μM and 0.67 μM, respectively. Compound 12 was a potential iron chelator and radical trapping antioxidant. Furthermore, compound 12 inhibited ferroptosis through down-regulating the expression of TXNIP gene.