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 Xinye Huang Xincai Hao Qun Zhou Weiguang Sun Changxing Qi Yonghui Zhang 

机构地区：[1]Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China [2]Institute of Organ Transplantation,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology Key Laboratory of Organ Transplantation,Ministry of Education,NHC Key Laboratory of Organ Transplantation,Key Laboratory of Organ Transplantation,Chinese Academy of Medical Sciences,Wuhan,Hubei 430030,China [3]Hubei Key Laboratory of Wudang Local Chinese Medicine Research,Hubei Engineering Technology Center for Comprehensive Utilization of Medicinal Plants,College of Pharmacy,Hubei University of Medicine,Shiyan,Hubei 442000,China

出　　处：《Chinese Journal of Chemistry》2024年第7期743-751,共9页中国化学（英文版）

基　　金：supported financially by the National Natural Science Foundation for Distinguished Young Scholars (No.81725021);the National Natural Science Foundation of China (Nos.82003633,82173705 and 31972865);the Natural Science Foundation of Hubei Province (2023AFB791);the Research and Development Program of Hubei Province (2020BCA058);the Open Foundation of Hubei Key Laboratory of Wudang Local Chinese Medicine Research (WDCM2023010).

摘　　要：Psoriasis is a chronic immune-mediated inflammatory skin disease and the TNF-αis 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,(36,5α,6α,22E)-5,6-epoxy-3-hydroxyergosta-8,22-dien-7-one(3)and calvasterol B(4),were iso-lated 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 path-ways 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-αinduced L929 cells death model,with the EC50 values of 49.85,46.75 and 4.99μmol/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-αin 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-αinhibitory agents in the clinical treatment of psoriasis.

关 键 词：Psoriasis Aspergillus sp.TJ507 TNF-α Ergosterol-polyether adducts Inflammatory skin disease 

分 类 号：TQ460.1[化学工程—制药化工]