一株南沙群岛柳珊瑚来源真菌 Aspergillus terreus 中化合物及 mPTPB 酶抑制活性研究

目的 从1株南沙群岛柳珊瑚来源真菌 Aspergillus terreus (NS02-09)中分离鉴定海洋天然产物,对所得化合物进行结核分枝杆菌酪氨酸磷酸激酶 (mPTPB) 抑制活性评价。方法 运用多种色谱手段分离纯化化合物,利用NMR、CD等现代波谱分析方法,对化合物进行结构鉴定、,通过衍生物制备获得两个乙酰化衍生物(2a和2b)；并对化合物2及其衍生物2a和2b进行mPTPB酶抑制活性测试。结果 鉴定了1个土曲霉酮(1)和1个丁烯酸内酯 (2) 的结构； 2具有较强的mPTPB酶抑制活性,而其乙酰化产物(2a和2b)的mPTPB 酶抑制活性显著降低。运用Sybyl X 1.3 软件,对2与mPTPB酶的模拟对接计算发现,丁烯酸内酯环及环上的羟基是化合物2发挥酶抑制活性的重要作用基团。结论 从柳珊瑚来源真菌 A. terreus (NS02-09) 中发现了具有mPTPB 酶抑制活性的丁烯酸内酯类化合物,并对其作用机制进行了计算研究,该类化合物的相关研究对抗结核药物先导化合物发现具有借鉴作用。

Compounds Isolated from Nansha Gorgonian Coral-derived Fungus Aspergillus terreus and their mPTPB Inhibitory Activity

Objective To isolate marine natural products from the gorgonian coral-derived fungus Aspergillus terreus (NS02-09) collected from the Nansha Island and evaluate the mycrobacterium tuberculosis protein tyrosine phosphatase B (mPTPB) inhibitory activity of these compounds. Methods The pure compounds were isolated by multiple chromatography methods and their structures were determined by modern spectroscopic methods, especially NMR and CD methods. The mPTPB inhibitory activities of 2 and its acetyl derivatives 2a and 2b were evaluated. Results The structures of 1 and 2 were identified. Additionally, compound 2 showed potent mPTPB inhibitory activity while its acetylated derivatives did not show any mPTPB inhibitory activity. The molecular docking result indicated that the lactone moiety and the hydroxy group in the lactone ring of 2 played important roles in binding with the active pocket of mPTPB. Conclusion A butyrolactone with potent mPTPB inhibitory activity was isolated from gorgonian coral-derived fungus A. terreus (NS02-09). This research supply important clue to find lead compounds in antituberculosis drugs discovery.