有机化学 ›› 2017, Vol. 37 ›› Issue (9): 2352-2360.DOI: 10.6023/cjoc201703048 上一篇    下一篇

研究论文

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

梅显贵a, 王立平b, 王冬阳a, 范杰a, 朱伟明a   

  1. a 中国海洋大学医药学院 海洋药物教育部重点实验室 青岛 266003;
    b 贵州医科大学 药物植物功效与利用国家重点实验室 贵阳 550014
  • 收稿日期:2017-03-28 修回日期:2017-04-27 出版日期:2017-09-25 发布日期:2017-05-10
  • 通讯作者: 朱伟明 E-mail:weimingzhu@ouc.edu.cn
  • 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

Mei Xianguia, Wang Lipingb, Wang Dongyanga, Fan Jiea, Zhu Weiminga   

  1. a Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003;
    b State Key Laborataory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014
  • Received:2017-03-28 Revised:2017-04-27 Online:2017-09-25 Published:2017-05-10
  • Contact: 10.6023/cjoc201703048 E-mail:weimingzhu@ouc.edu.cn
  • 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23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24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

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.

Key words: polycyclic tetramate macrolactams, Actinoalloteichus cyanogriseus, antitumor, antifugus