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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2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。
OBJECTIVE To isolate and identify natural marine products from Aspergillus terreus (NS02-09) of a genus Salix in the Nansha Islands and to evaluate the inhibitory activity of mycobacterium tuberculosis tyrphosphate kinase (mPTPB). Methods The compounds were isolated and purified by many chromatographic methods. The structures of the compounds were identified by modern spectroscopic methods such as NMR and CD. Two acetylated derivatives (2a and 2b) were obtained by the method of derivatization. Compounds 2 and their derivatives Articles 2a and 2b were tested for mPTPB enzyme inhibitory activity. As a result, the structures of 1 terfenamicone (1) and 1 butenolide (2) were identified; 2 has strong mPTPB enzyme inhibitory activity whereas the mPTPB enzyme inhibitory activity of its acetylated products (2a and 2b) Significantly lower. Sybyl X 1.3 software was used to simulate the docking of mPTPB with mPTPB. It was found that the intramolecular lactone ring and the hydroxyl group on the ring are important groups for the enzyme 2 to exert its inhibitory activity. CONCLUSION: The crotonolactones with mPTPBase inhibitory activity were found from A. terreus (NS02-09), and the mechanism of action was studied. Lead compounds found to have reference.