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

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2023-04, Vol.86 (4), p.830-841
• Main Authors: Li, Yuanli, Shi, Jiayi, Liu, Ruzhen, Liu, Yu, Liu, Ruifeng, Wu, Zongmin, Xu, Wei, Ma, Huabin, Luo, Hai-Bin, Cheng, Zhongbin
• Format: Article
• Language: English
• Subjects: Aspergillus - chemistry; Ferroptosis; Hydrogen Peroxide; Molecular Structure; Monocyclic Sesquiterpenes; Phenols - pharmacology; Sesquiterpenes - chemistry
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.2c01022

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 EC50 values ranging from 2 to 4 μM, while it exhibited no effects on TNFα-induced necroptosis or H2O2-induced cell necrosis.