Cytotoxic Thiodiketopiperazine Derivatives from the Deep Sea-Derived Fungus Epicoccum nigrum SD-388
Cytotoxic Thiodiketopiperazine Derivatives from the Deep Sea-Derived Fungus Epicoccum nigrum SD-388
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DOI：
10.3390/md18030160
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发表时间：
2020-03-01
期刊：
影响因子：
5.4
通讯作者：
Wang, Bin-Gui
中科院分区：
文献类型：
--
作者：
Chi, Lu-Ping;Li, Xiao-Ming;Wang, Bin-Gui
四种新的硫代二酮哌嗪生物碱，即5 ′-羟基-6 ′-烯-epicoccin G（1），7-甲氧基-7 ′-羟基epicoccin G（2），8 ′-乙酰氧基epicoccin D（3）和7 ′-去甲氧基rostratin C（4），以及一对新的对映体二酮哌嗪，（+/-）-5-羟基二苯基氮杂萘A（5），沿着五种已知的类似物（6-10），从深海沉积物（~ 4500 m）真菌Epicoccum nigrum SD-388的培养物提取物中分离并鉴定了10个菌株。它们的结构是建立在详细解释的NMR光谱和质谱数据的基础上。X射线晶体学分析证实了化合物1-3的结构并建立了化合物1-3的绝对构型，而化合物4和5的绝对构型通过ECD计算确定。化合物4和10显示出对Huh 7.5肝肿瘤细胞的有效活性，其与阳性对照索拉非尼的活性相当，并且C-2/C-2'处的二硫键可能是活性所必需的。
Four new thiodiketopiperazine alkaloids, namely, 5'-hydroxy-6'-ene-epicoccin G (1), 7-methoxy-7'-hydroxyepicoccin G (2), 8'-acetoxyepicoccin D (3), and 7'-demethoxyrostratin C (4), as well as a pair of new enantiomeric diketopiperazines, (+/-)-5-hydroxydiphenylalazine A (5), along with five known analogues (6-10), were isolated and identified from the culture extract of Epicoccum nigrum SD-388, a fungus obtained from deep-sea sediments (-4500 m). Their structures were established on the basis of detailed interpretation of the NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis confirmed the structures and established the absolute configurations of compounds 1-3, while the absolute configurations for compounds 4 and 5 were determined by ECD calculations. Compounds 4 and 10 showed potent activity against Huh7.5 liver tumor cells, which were comparable to that of the positive control, sorafenib, and the disulfide bridge at C-2/C-2' is likely essential for the activity.