Asperustins A–J: Austocystins with Immunosuppressive and Cytotoxic Activities from <i>Aspergillus ustus</i> NRRL 5856
Jinling Chang, Yutian Gan, Yin-Hui Zhou, Xiaogang Peng, Zuo-Ye Xie, Xiang‐Gao Meng, Shu‐Ming Li, Hanli Ruan
Abstract
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.