海洋异壁放线菌WH1-2216-6产生的多环含特特拉姆酸大环内酰胺
收稿日期: 2017-03-28
修回日期: 2017-04-27
网络出版日期: 2017-05-10
基金资助
国家自然科学基金（Nos.81561148012，41376148）和国家自然科学基金-广东联合基金（No.U1501221）资助项目.
Polycyclic Tetramate Macrolactams from the Marine-Derived Actinoalloteichus cyanogriseus WH1-2216-6
Received date: 2017-03-28
Revised date: 2017-04-27
Online published: 2017-05-10
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 81561148012, 41376148) and the National Natural Science Foundation of China-Guangdong Fund Joint Project (No. U1501221).
采用紫外跟踪分离和波谱鉴定的方法，从海洋异壁放线菌（Actinoalloteichus cyanogriseus WH1-2216-6）的发酵产物中分离鉴定了6个5，5，6-多环含特特拉姆酸大环内酰胺（PTMs）类天然产物：16-hydroxymaltophilin（1）、dihydromaltophilin（2）、4-deoxydihydromaltophilin（3）、maltophilin（4）、xanthobaccin C（5）和FI-2（6），其中1为新化合物.评价了化合物1~5对人正常肝细胞L-02及人癌细胞A549、MCF-7、Jurkat、BXPC-3、HCT-116、PANC-1和K562的细胞毒活性，结果表明：化合物1~5对上述人癌细胞具有细胞毒活性，其半数抑制浓度（IC50）为0.1~9.7 μmol·L-1；新化合物1对L-02的毒性较低，但对Jurkat、HCT-116和BXPC-3的选择指数（SI）分别高达31.5、41.1和52.4.除化合物2和3对A549和MCF-7的肿瘤细胞毒活性外，其余的肿瘤细胞毒活性是首次报道.还测试了化合物1~6的抗烟曲霉活性，发现化合物2和4的活性较好，其最小抑菌浓度（MIC）分别为3.04和6.12 μmol·L-1，这是首次发现5，5，6-PTMs类化合物具有抗烟曲霉活性.
关键词： 异壁放线菌; 5,5,6-多环含特特拉姆酸大环内酰胺; 抗肿瘤活性; 抗烟曲霉活性
梅显贵 , 王立平 , 王冬阳 , 范杰 , 朱伟明 . 海洋异壁放线菌WH1-2216-6产生的多环含特特拉姆酸大环内酰胺[J]. 有机化学, 2017 , 37(9) : 2352 -2360 . DOI: 10.6023/cjoc201703048
From the fermentation broth of the marine-derived Actinoalloteichus cyanogriseus WH1-2216-6, a new 5,5,6-polycyclic tetramate macrolactam (PTM) named 16-hydroxymaltophilin (1) was isolated and identified along with five known analouges, dihydromaltophilin (2), 4-deoxydihydromaltophilin (3), maltophilin (4), xanthobaccin C (5) and FI-2 (6), by means of UV-guided isolation as well as the spectroscopic identification. The cytotoxicities of compounds 1~5 were tested against the human normal hepatic cell line (L-02) and the seven human cancer cell lines, A549, MCF-7, Jurkat, BXPC-3, HCT-116, PANC-1 and K562. The results showed that compounds 1~5 were active against the above human cancer cell lines with the IC50 values of 0.1~9.7 μmol·L-1, among which the new compound 1 was the lowest toxic to L-02 cell and the most selective to Jurkat, HCT-116 and BXPC-3 cells with the selection index (SI) of 31.5, 41.4 and 52.4, respectively. The antifungal activities of 1~6 against Aspergillus fumigatus AF293 were also tested by two-fold dilution method. Compounds 2 and 4 were active against A. fumigatus AF293 with the minimum inhibitory concentration (MIC) values of 3.04 and 6.12 μmol·L-1, respectively. To the best of our knowledge, this is the first time to report the antifungal activity of 5,5,6-PTMs against A. fumigatus AF293. Apart from the cytotoxicity of compounds 2 and 3 against A549 and MCF-7 tumor cells lines, the other cytotoxicities were reported here for the first time, indicating the potential use of PTMs as the antitumor and antifungal lead compounds against A. fumigatus.
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