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, [Rh 2 (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 IC 50 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 IC 50 values of 3.9, 1.3, 0.46, and 2.3 μM, respectively.