无花果内生菌Alternaria sp.QDFB-2发酵液的聚酮类化学成分研究

Polyketide compounds in the liquid culture of endophyte Alternaria sp.QDFB-2 from Ficus carica L.

  • 摘要:
    目的 研究无花果内生菌Alternaria sp.QDFB-2发酵液的聚酮类化学成分及其体外细胞毒活性。
    方法 综合采用硅胶柱、Sephadex LH-20凝胶柱、ODS反相柱和高效液相色谱法等方法对Alternaria sp.QDFB-2发酵液的化学成分进行分离纯化, 再利用核磁共振谱(NMR)、高分辨质谱(HR-MS)等现代波谱技术和文献比对方法鉴定化合物结构,最后采用四甲基偶氮唑蓝(MTT)法测定化合物的体外细胞毒活性。
    结果 从Alternaria sp.QDFB-2发酵液乙酸乙酯粗浸膏中共分离得到7个聚酮类化合物,分别为7-hydroxy-2, 5-dimethyl-4H-1-benzopyran-4-one (1)、1-deoxyrubralactone (2)、alternariol-9-O-monomethyl ether (3)、alternariol (4)、altenuisol (5)、stemphyperylenol (6)和altertoxin Ⅰ(7)。体外细胞毒活性测定结果表明,化合物4对人宫颈癌细胞株HeLa和人肝癌细胞株SMMC-7721具有显著的增殖抑制活性,半抑制浓度(IC50)分别为13.43和50.47 μg/mL。
    结论 Alternaria sp.QDFB-2能产生丰富的聚酮类化合物,极具开发微生物药物的研究价值。

     

    Abstract:
    Objective To investigate the polyketide compounds in the liquid culture of endophyte Alternaria sp.QDFB-2 from Ficus carica L. and evaluate their in vitro cytotoxicity.
    Methods The chemical constituents in the fermentation broth of Alternaria sp.QDFB-2 were fractionated and purified through multiple chromatographic methods such as silica gel column, Sephadex LH-20 gel column, ODS reserved phase columnand high performance liquid chromatography. Then, structures of obtained compounds were determined by modern spectroscopy methods including nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HR-MS) and comparison with literature. Finally, the cytotoxicity of these compounds was evaluated by Methyl Thiazolyl Tetrazolium (MTT) method.
    Results Seven polyketide compounds were obtained from the crude extract of liquid culturefrom Alternaria sp.QDFB-2 and identified as 7-hydroxy-2, 5-dimethyl-4H-1-benzopyran-4-one (1), 1-deoxyrubralactone (2), alternariol-9-O-monomethyl ether (3), alternariol (4), altenuisol (5), stemphyperylenol (6) and altertoxin Ⅰ (7), respectively. The in vitro cytotoxicity assay showed that compound 4 had significant inhibition activity against human cervical carcinoma cell line HeLa and human hepatocellular carcinoma cell line SMMC-7721, with half-maximal inhibitory concentration (IC50) values of 13.43 and 50.47 μg/mL, respectively.
    Conclusion Alternaria sp.QDFB-2 could produce abundant polyketide compounds, which is worthy of further research in developing drugs from microorganism.

     

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