北部湾海洋真菌Aspergillus fumigatus DL-p0m-g2的化学成分及药理活性研究

Study on the chemical constituents and pharmacological activity of the marine-derived fungus Aspergillus fumigatus DL-p0m-g2 in the Beibu Gulf

为获得具有生物活性的化合物,对一株分离于北部湾钉螺菌株Aspergillus fumigatus DL-p0m-g2的化学成分及药理活性进行研究。综合应用反相ODS(octadecylsilyl)柱色谱、半制备液相等多种色谱学方法进行分离纯化,根据化合物理化性质、质谱和核磁共振波谱学数据进行结构鉴定,并对分离得到的化合物进行细胞毒活性、抑菌活性和胆固醇转运蛋白NPC1L1(NPC1-like intracellular cholesterol transporter 1)蛋白结合等生物活性评价。实验共分离得到21个生物碱类化合物和1个甾体,分别鉴定为6-methoxyspirotryprostatin B(1)、spirotryprostatin A(2)、fumitremorgin C(3)、cyclotryprostatin A(4)、fumitremorgin B(5)、pseurotin A(6)、azaspirofuran A(7)、azaspirofuran B(8)、cephalimysin C(9)、cephalimysin B(10)、fumiquinazoline C(11)、fumiquinazoline B(12)、fumiquinazoline A(13)、fumiquinazoline D(14)、fumiquinazoline F(15)、tryprostatin B(16)、verruculogen(17)、chaetominine(18)、bisdethiobis(methylthio)glitoxin(19)、helvolic acid(20)、7-deacetylpyripyropene A(21)、terezine D(22)。其中化合物6对人肝癌细胞(Hep G2)、人肺癌细胞(A549)、人直肠癌细胞(HCT116)有一定的细胞毒活性;化合物1、3和20对金黄色葡萄球菌表现出抑菌活性;化合物14与NPC1L1蛋白具有较好的结合,显示其在降脂药物开发中的研究潜力。

The chemical constituents and their bioactivities of Aspergillus fumigatus DL-p0m-g2 from the Beibu Gulf were studied in order to obtain bioactive compounds.The compounds were isolated and purified by reversed-phase ODS column chromatography,semi-preparative liquid chromatography and other chromatographic methods.Their structures were identified by physicochemical properties,mass spectrometry and nuclear magnetic resonance spectroscopy.The cytotoxic,antibacterial and cholesterol transporter NPC1L1 protein binding activities of the isolated compounds were evaluated.As a result,a total of 21 alkaloids and one steroid were isolated and identified as 6-methoxyspirotryprostatin B(1),spirotryprostatin A(2),fumitremorgin C(3),cyclotryprostatin A(4),fumitremorgin B(5),pseurotin A(6),azaspirofuran A(7),azaspirofuran B(8),cephalimysin C(9),cephalimysin B(10),fumiquinazoline C(11),fumiquinazoline B(12),fumiquinazoline A(13),fumiquinazoline D(14),fumiquinazoline F(15),tryprostatin B(16),verruculogen(17),chaetominine(18),bisdethiobis(methylthio)glitoxin(19),helvolic acid(20),7-deacetylpyripyropene A(21),terezine D(22).Compound 6 showed moderate cytotoxic activity against human hepatoma cells(HepG2),human lung cancer cells(A549)and human rectal cancer cells(HCT116).Compounds 1,3 and 20 showed antibacterial activity against Staphylococcus aureus.Compound 14 showed a good binding with NPC1L1 protein,indicating its potential in the development of lipid-lowering drugs.