Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica/Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, Guangdong, China.
New Drug Research & Development Co., Ltd, North China Pharmaceutical Group Corporation, Shijiazhuang, Hebei 050015, China.
Bioorg Chem. 2021 Feb;107:104571. doi: 10.1016/j.bioorg.2020.104571. Epub 2020 Dec 19.
Nine new xanthone-type and anthraquinone-type mycotoxins including austocystins J-N (1-5), 7-chloro versicolorin A (6), 3'-hydroxy-8-O-methyl versicolorin B (7), 8-O-methyl versiconol (8) and 2',3'-dihydroxy versiconol (9), together with 17 known analogues (10-26) were isolated from an extract of the deep-sea-derived fungus Aspergillus puniceus SCSIO z021. Their structures were elucidated by detailed analysis of spectroscopic data, and their absolute configurations were further determined by quantum chemical calculations of ECD spectra or comparison of the experimental ECD spectra. Eleven hydrogenated austocystins were synthesized from 1-2, 10-15 and 17 by catalytic hydrogenation for bioactivities evaluation. Totally, 18 of the all 37 compounds showed strong toxicity against brine shrimps or Vero cell, and the toxicity of 8-O-methyldemethylsterigmatocystin (18) (LC = 0.020 µM) against brine shrimps was higher than those of three positive controls. In addition, 22 of the isolated compounds also exhibited significant inhibitory activity against seven different protein tyrosine phosphatases (PTPs), among them austocystin H (15) and methyl-averantin (24) were the most potent inhibitors with IC values of 0.20-3.0 µM. Their structure-bioactivity relationship was also discussed.
从深海来源的真菌棘孢曲霉 SCSIO z021 的提取物中分离得到了 9 种新的黄烷酮型和蒽醌型霉菌毒素，包括 austocystins J-N（1-5）、7-氯 versicolorin A（6）、3'-羟基-8-O-甲基 versicolorin B（7）、8-O-甲基 versiconol（8）和 2',3'-二羟基 versiconol（9），以及 17 种已知类似物（10-26）。通过详细分析光谱数据阐明了它们的结构，并通过量子化学计算 ECD 光谱或比较实验 ECD 光谱进一步确定了它们的绝对构型。从 1-2、10-15 和 17 通过催化氢化合成了 11 种氢化 austocystins，用于生物活性评价。在所有 37 种化合物中，共有 18 种对卤虫或 Vero 细胞具有很强的毒性，8-O-甲基去甲瘤菌素（18）（LC = 0.020 µM）对卤虫的毒性高于三种阳性对照物。此外，分离得到的 22 种化合物对 7 种不同的蛋白酪氨酸磷酸酶（PTPs）也表现出显著的抑制活性，其中 austocystin H（15）和甲基 averantin（24）是最有效的抑制剂，IC 值为 0.20-3.0 µM。还讨论了它们的结构-生物活性关系。
