Structure Revisions of Phenolic Bisabolane Sesquiterpenes and a Ferroptosis Inhibitor from the Marine-Derived Fungus Aspergillus versicolor YPH93.

Seven new phenolic bisabolane sesquiterpenoids ( 1 - 7 ), along with 10 biogenetically related analogues ( 8 - 17 ), were obtained from the deep-sea-derived fungus Aspergillus versicolor YPH93. The structures were elucidated based on extensive analyses of the spectroscopic data. Compounds 1 - 3 are the first examples of phenolic bisabolanes that contain two hydroxy groups attached to the pyran ring. The structures of sydowic acid derivatives ( 1 - 6 and 8 - 10 ) were carefully studied, leading to the structure revisions of six known analogues, including a revision of the absolute configuration for sydowic acid ( 10 ). All metabolites were evaluated for their effects on ferroptosis. Compound 7 exerted inhibition on erastin/RSL3-induced ferroptosis with EC 50 values ranging from 2 to 4 μM, while it exhibited no effects on TNFα-induced necroptosis or H 2 O 2 -induced cell necrosis.