Asperustins A-J: Austocystins with Immunosuppressive and Cytotoxic Activities from Aspergillus ustus NRRL 5856
- J Nat Prod. 2024 Apr 26;87(4):966-975. doi: 10.1021/acs.jnatprod.3c01243.
- 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Wuhan 430030, People's Republic of China.
- 2. Xiangyang Hospital of Traditional Chinese Medicine, Xiangyang 441000, People's Republic of China.
- 3. College of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of China.
- 4. Institut für Pharmazeutische Biologie und Biotechnologie, Fachbereich Pharmazie, Philipps-Universität Marburg, Robert-Koch Straße 4, 35037 Marburg, Germany.
Ten new (1-10) and nine known (11-19) austocystins, along with four known Anthraquinones (20-23), were isolated from the culture of Aspergillus ustus NRRL 5856 by bioactivity-guided fractionation. The structures of the new compounds were elucidated by spectroscopic data analysis, X-ray crystallographic study, the modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of the similar analogues. Compounds 1-8 represent the first examples of austocystins with a C-4' oxygenated substitution. The absolute configuration of 1″-hydroxy austocystin D (11) was determined by single-crystal X-ray diffraction and consideration of its biosynthetic origin. Compounds 5, 9, and 11 exhibited significant inhibitory effects against the proliferation of ConA-induced T cells with IC50 values of 1.1, 1.0, and 0.93 μM, respectively. Furthermore, these compounds suppressed the expression of IL-6 in a dose-dependent manner. Compounds 10-12 and 14 showed pronounced cytotoxicities against MCF-7 with IC50 values of 3.9, 1.3, 0.46, and 2.3 μM, respectively.