内生真菌Alternaria tenuissima PC-005抗耐药菌活性成分研究

Anti-resistant bacteria components from the metabolites of endophytic Alternaria tenuissima PC-005

目的研究内生真菌Alternaria tenuissima PC-005次生代谢产物抗耐药菌的活性成分。方法采用硅胶色谱、羟丙基葡聚糖凝胶柱色谱、高效液相色谱等分离纯化手段对内生真菌PC-005次生代谢物进行分离纯化,利用MS、1H-NMR、13C-NMR等现代波谱分析技术对分离得到的单体化合物进行结构鉴定;采用96孔板法测试单体化合物对临床耐药菌的抗菌活性。结果从内生真菌PC-005次生代谢物的活性组分中分离得到7个化合物,分别为5-甲氧基格链孢酚(1)、格链孢酚(2)、对羟基苯乙酮(3)、β-谷甾醇3-O-β-D-葡萄糖苷-6'-O-棕榈酸酯(4)、β-腺苷(5)、细格菌素(6)和十八碳二烯酸(7)。化合物1、6和7对多重耐药肺炎克雷伯杆菌、普通变形杆菌、表皮葡萄球菌、大肠埃希菌、金黄色葡萄球菌、奇异变形杆菌、屎肠球菌和鲍曼不动杆菌有抑制作用,最低抑菌浓度为62.5~500μg·m L-1。结论化合物3~7均为从内生菌Alternaria tenuissima代谢物中首次分离。化合物1、6和7为内生真菌Alternaria tenuissima PC-005抗耐药菌的活性成分。

Objective To determine the anti-resistant bacteria components from the metabolites of endophytic Alternaria tenuissima PC-005. Methods The active components ofAlternaria tenuissima PC-005 were isolated and purified by modern separation techniques. Their structures were identified by spectroscopic methods including MS and NMR analysis. The antibacterial activity was tested on a 96-well plate. Results Seven compounds were isolated from the extracted metabolites of Alternaria tenuissima PC-005. The compounds were identified as alternariol 5-O-methyl ether （1）, alternariol （2）, p-hydroxyacetophenone （3）, β-sitosteryl-3β- glucopyranoside-6＇-O-palmitate （4）, fl-adenosine （5）, altenusin （6）, and linoleicacid （7）. Anti-resistant bacteria activities showed that compounds 1, 6 and 7 were against multidrug-resistant Klebsiella pneumoniae, Proteus vulgaris, Staphylococcus epidermidis, Escherichia coli, Staphylococcus aureus, Proteus mirabilis, Enterococcus faecium, and Acinetobacter baumannii with minimum inhibitory concentration ranging from 62.5 to 500 μg · mL-1. Conclusion Compounds 3 - 7 have been isolated from the metabolites ofAlternaria tenuissima for the first time. Compounds 1, 6 and 7 are the main active components ofAlternaria tenuissima PC-005.