毒菇来源真菌 Penicillium sp.YNJ-22中嗜氮酮类化合物及其活性研究
Studies on azaphilones isolated from the fungus Penicillium sp.YNJ-22 derived from wild poisonous mushroom and their bioactivities
宫鹤翔 1赵雪 2王紫临 1康亚帅 3鹿跃 4郭润东 5张国刚 6李长伟2
作者信息
- 1. 沈阳药科大学中药学院,辽宁沈阳 110016;军事医学研究院毒物药物研究所抗毒药物与毒理学国家重点实验室,北京 100850
- 2. 军事医学研究院毒物药物研究所抗毒药物与毒理学国家重点实验室,北京 100850
- 3. 军事医学研究院毒物药物研究所抗毒药物与毒理学国家重点实验室,北京 100850;南京中医药大学药学院,江苏南京 210046
- 4. 军事医学研究院毒物药物研究所抗毒药物与毒理学国家重点实验室,北京 100850;长春中医药大学药学院,吉林长春 130117
- 5. 军事医学研究院毒物药物研究所抗毒药物与毒理学国家重点实验室,北京 100850;青岛大学药学院,山东青岛 266071
- 6. 沈阳药科大学中药学院,辽宁沈阳 110016
- 折叠
摘要
目的 研究毒菇致命鹅膏(Amanita exitialis Zhu L.Yang &T.H.Li)来源青霉属(Penicillium)真菌Peni-cillium sp.YNJ-22的次级代谢产物,并对其生物活性进行初步评价.方法 采用硅胶柱色谱、ODS柱色谱、高效液相色谱等分离技术对菌株Penicillium sp.YNJ-22的发酵产物进行分离纯化,运用核磁共振、质谱等波谱学方法鉴定化合物结构,采用噻唑蓝比色法评价其细胞毒活性,采用微量肉汤稀释法测试其抑菌活性.结果 与结论从真菌Penicillium sp.YNJ-22发酵产物中分离鉴定出10个嗜氮酮类化合物,分别为(11E)-isochro-mophilone Ⅳ(1)、(11Z)-isochromophilone Ⅳ(2)、epi-isochromophilone Ⅲ(3)、sclerotioramine(4)、penicilphi-lone A(5)、geumsanol F(6)、WB(7)、geumsanol G(8)、penicilazaphilone B(9)和 geumsanol D(10).细胞毒活性测试结果显示:化合物1对人肺癌细胞(A549)、人乳腺癌细胞(MCF-7)和小鼠小胶质细胞(BV2)均具有较强的细胞毒活性[IC50=(27.37±0.13)、(22.35±9.55)、(26.92±1.00)μmol.L-1],化合物 4 对 A549 和MCF-7细胞具有一定的细胞毒活性[IC50=(30.74±2.02)、(34.58±2.45)μmol·L-1].抑菌活性测试结果显示:化合物2和3对金黄色葡萄球菌的生长具有一定的抑制作用(MIC分别为128、64 μg·mL-1).本研究是对致命鹅膏共附生真菌次级代谢产物的首次报道,其中化合物1的细胞毒活性与化合物2的抑菌活性为首次报道.
Abstract
The secondary metabolites,isolated from the fungus Penicillium sp.YNJ-22 derived from wild poisonous mushroom Amanita exitialis,and their bioactivities were studied.Ten azaphilones were isolated by multiple separation techniques,and the isolated compounds were identified by spectral data(mass spectrometry,nuclear magnetic resonance)as(11E)-isochromophilone Ⅳ(1),(11Z)-isochromophilone Ⅳ(2),epi-isochromophilone Ⅲ(3),sclerotioramine(4),penicilphilone A(5),geumsanol F(6),WB(7),geumsanol G(8),penicilazaphilone B(9)and geumsanol D(10).The cytotoxic activities were assayed by MTT method and the antibacterial activities were assayed by broth microdilution method.The cytotoxic activities assay showed that compound 1 displayed stronger cytotoxic activities against human lung cancer cells(A549),human breast cancer cells(MCF-7)and mouse microglia cells(BV2)[IC50=(27.37±0.13),(22.35±9.55),(26.92±1.00)μmol·L-1].Compound 4 displayed some cytotoxic activities against A549 and MCF-7 cells[IC50=(30.74±2.02),(34.58±2.45)pmnol L-1].The antibacterial activities test showed that compounds 2(MIC=128 μg·mL-1)and 3(MIC=64 μg·mL-1)exhibited some inhibitory effects on Staphylococcus aureus.The secondary metabolites of the epiphytic fungi derived from Amanita exitialis were reported for the first time,and the cytotoxic activity of compound 1 and the antibacterial activity of compound 2 were also reported for the first time.
关键词
嗜氮酮/青霉属/共附生真菌/次级代谢产物/生物活性Key words
azaphilones/Penicillium/endophytic fungi/secondary metabolite/biological activity引用本文复制引用
出版年
2024