Asperustins A–J: Austocystins with Immunosuppressive and Cytotoxic Activities from Aspergillus ustus NRRL 5856

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.