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

作　　者：宫鹤翔 赵雪 王紫临 康亚帅 鹿跃 郭润东 张国刚[1] 李长伟 GONG Hexiang;ZHAO Xue;WANG Zilin;KANG Yashuai;LU Yue;Guo Rundong;ZHANG Guogang;LI Changwei(School of Traditional Chinese Materia Medica,Shenyang Pharmaceutical University,Shenyang 110016,China;State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China;School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210046,China;School of Pharmacy,Changchun University of Chinese Medicine,Changchun 130117,China;School of Pharmacy,Qingdao University,Qingdao 266071,China)

机构地区：[1]沈阳药科大学中药学院,辽宁沈阳110016 [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]南京中医药大学药学院,江苏南京210046 [4]长春中医药大学药学院,吉林长春130117 [5]青岛大学药学院,山东青岛266071

出　　处：《中国药物化学杂志》2024年第2期110-119,共10页Chinese Journal of Medicinal Chemistry

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Penicillium 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)-isochromophiloneⅣ(1)、(11Z)-isochromophiloneⅣ(2)、epi-isochromophiloneⅢ(3)、sclerotioramine(4)、penicilphilone 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[IC_(50)=(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[IC_(50)=(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、64μg·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。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 II(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)[IC_(50)=(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[IC_(50)=(30.74±2.02),(34.58±2.45)μmol·L^(-1)].The antibacterial activities test showed that compounds 2(MIC=128μg·mL^(-1))and 3(MIC=64μg·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 

分 类 号：R284[医药卫生—中药学]