Polyaspers A and B, the First Ergosterol‐Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus sp. TJ507

作者：Hong Hu, Lanqin Li, Zhengyi Shi, Xueqi Lan, Yeting Zhang, Yeting Zhang, Xinye Huang, Xincai Hao, Qun Zhou, Weiguang Sun, Changxing Qi, Yonghui Zhang, Yonghui Zhang · 发表于：Chinese Journal of Chemistry · 年份：2023 · DOI：10.1002/cjoc.202300649 · 被引用次数：8 · 研究领域：Fungal Biology and Applications、Microbial Natural Products and Biosynthesis、Antifungal resistance and susceptibility

Comprehensive Summary Psoriasis is a chronic immune‐mediated inflammatory skin disease and the TNF‐ α is an important therapeutic target of this disease. In our continuous study of bioactive natural products from fungi, the first ergosterol‐polyether adducts, polyaspers A ( 1 ) and B ( 2 ), along with two known ergosterols, (3 β ,5 α ,6 α ,22 E )‐5,6‐epoxy‐3‐hydroxyergosta‐8,22‐dien‐7‐one ( 3 ) and calvasterol B ( 4 ), were isolated from Aspergillus sp. TJ507. Structure elucidation was accomplished by extensive spectroscopic analysis and single‐crystal X‐ray diffraction tests. Polyaspers A and B possessing an unequalled 6/6/6/5/5/6/6/6/6 nonacyclic system, and their biosynthetic pathways were proposed to include intermolecular cyclization and Diels‐Alder reactions. Activity screen of these isolates showed that 1 — 3 could improve the cell viability in an actinomycin D/TNF‐ α induced L929 cells death model, with the EC 50 values of 49.85, 46.75 and 4.99 μmol/L, respectively, and the activity of 3 was even comparable with that of the positive control SPD304. Further bioactive investigations discovered 3 could suppress the inflammatory response simulated with TNF‐ α in HaCaT cells. In an imiquimod‐induced psoriasis murine model, 3 significantly restrained the development of psoriasis symptoms and reduced the expression of IL‐17 and IL‐23, presenting an anti‐psoriatic effect. As such, those ergosterol derivatives, might serve as lead compounds for the development of novel TNF‐ α ...