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
Hong Hu
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
‡ These authors contributed equally to this work.
Search for more papers by this authorLanqin Li
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
‡ These authors contributed equally to this work.
Search for more papers by this authorZhengyi Shi
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
‡ These authors contributed equally to this work.
Search for more papers by this authorXueqi Lan
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
Search for more papers by this authorYeting Zhang
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
Search for more papers by this authorXinye Huang
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
Search for more papers by this authorXincai Hao
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
Search for more papers by this authorQun Zhou
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
Search for more papers by this authorCorresponding Author
Weiguang Sun
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
E-mail: [email protected]; [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Changxing Qi
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
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
E-mail: [email protected]; [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Yonghui Zhang
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
E-mail: [email protected]; [email protected]; [email protected]Search for more papers by this authorHong Hu
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
‡ These authors contributed equally to this work.
Search for more papers by this authorLanqin Li
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
‡ These authors contributed equally to this work.
Search for more papers by this authorZhengyi Shi
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
‡ These authors contributed equally to this work.
Search for more papers by this authorXueqi Lan
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
Search for more papers by this authorYeting Zhang
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
Search for more papers by this authorXinye Huang
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
Search for more papers by this authorXincai Hao
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
Search for more papers by this authorQun Zhou
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
Search for more papers by this authorCorresponding Author
Weiguang Sun
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
E-mail: [email protected]; [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Changxing Qi
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
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
E-mail: [email protected]; [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Yonghui Zhang
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 China
E-mail: [email protected]; [email protected]; [email protected]Search for more papers by this authorComprehensive 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, (3β,5α,6α,22E)-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 EC50 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 inhibitory agents in the clinical treatment of psoriasis.
Supporting Information
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Appendix S1: Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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