1株黄河三角洲来源杂色曲霉A.versicolor BHT-72的次级代谢产物研究  

Studies on the secondary metabolites of A. versicolor BHT-72 isolated from the Yellow River Delta

作　　者：司婕 倪娜[2] 刘孟珊 贺倩倩[3] 张臻[2] 苗双[2] 满玉清[3] 宫凯凯 SI Jie;NI Na;LIU Meng-shan;HE Qian-qian;ZHANG Zhen;MIAO Shuang;MAN Yu-qing;GONG Kai-kai(School of Pharmacy,Binzhou Medical University,Yantai 264003,China;Medical Research Center,Binzhou Medical University Hospital,Binzhou 256603,China;Department of Pharmacy,Binzhou Medical University Hospital,Binzhou 256603,China;Department of Pharmacy,Binzhou Youfu Hospital,Binzhou 256613,China)

机构地区：[1]滨州医学院药学院,山东烟台264003 [2]滨州医学院附属医院医学研究中心,山东滨州256603 [3]滨州医学院附属医院药学部,山东滨州256603 [4]滨州市优抚医院药剂科,山东滨州256613

出　　处：《中国海洋药物》2023年第1期31-36,共6页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金项目(81903537);山东省自然科学基金项目(ZR2018BB024);山东省中医药科技发展计划项目(2019-0521);滨州医学院科技计划项目(BY2017KJ17)资助。

摘　　要：目的 研究1株黄河三角洲盐碱地曲霉属真菌A. versicolor BHT-72的次级代谢产物及其生物活性。方法 采用硅胶柱层析、Sephadex LH-20葡聚糖凝胶柱层析、ODS柱层析、高效液相(HPLC)等色谱方法对该菌株的次级代谢产物分离纯化,并通过核磁共振(NMR)、质谱(MS)等方法,结合相关文献对比鉴定化合物结构;分别采用CCK8法和改良的Ellman法对化合物进行抗肿瘤和抗乙酰胆碱酯酶抑制活性的测试。结果 从A. versicolor BHT-72的大米发酵产物中共分离得到10个单体化合物,分别为diorcinol(1)、12-O-acetyl-sydowinin A(2)、sydowinin A(3)、13-O-acetylsydowinin B(4)、sydoxanthone(5)、3-formylindole(6)、尿苷(7)、zarzissine(8)、6-氨基嘌呤核苷(9)、6-氨基嘌呤脱氧核苷(10)。细胞毒活性测定结果显示,化合物1在质量浓度为30μg/mL时,对鼻咽癌细胞CNE-2的抑制率为65.0%,对非小细胞肺癌H1299和H520的抑制率分别为81.3%和87.0%。化合物2在质量浓度为30μg/mL时对H1299细胞的抑制率为49.8%。在质量浓度为100μg/mL时,化合物1~5对乙酰胆碱酯酶具有一定的抑制活性,抑制率分别为59.4%、60.0%、54.6%、40.0%和66.6%。结论 黄河三角洲盐碱地真菌A. versicolor BHT-72能产生结构多样的活性次级代谢产物,化合物1和2对鼻咽癌细胞CNE-2、非小细胞肺癌H1299和H520具有一定的细胞毒活性,化合物1~5具有一定的乙酰胆碱酯酶抑制活性。Objective To study the secondary metabolites and biological activities of a strain A. versicolor BHT-72 from saline-alkali soil in the Yellow River Delta. Methods By means of various kinds of chromatography including silica gel, Sephadex LH-20, ODS and high-performance liquid chromatography(HPLC), the secondary metabolites of the strain were isolated and purified, and the structures of the compounds were identified by nuclear magnetic resonance(NMR) and mass spectrometry(MS) combined with the relevant literatures.The anti-tumor and anti-acetylcholinesterase inhibitory activities of the compounds were tested by CCK8 method and modified Ellman’s method respectively. Results Ten compounds were isolated from the rice fermentation of A. versicolor BHT-72, which were identified as diorcinol(1), 12-O-acetyl-sydowinin A(2),sydowinin A(3), 13-O-acetylsydowinin B(4), sydoxanthone(5), 3-formylindole(6), uridine(7), zarzissine(8),6-amino-9-β-D-ribofuranosyl-9H-purine(9),2’-Deoxyadenosine(10). The cytotoxic activity results showed that compound 1, at the concentration of 30 μg/mL, showed cytotoxicities toward nasopharyngeal carcinoma cells CNE-2, non-small cell lung cancer cells H1299 and H520 with the inhibition rate of 65.0%, 81.3%and 87.0%, respectively. The inhibition rate of compound 2 on H1299 cells was 49.8% at 30 μg/mL. At the concentration of 100 μg/mL, compounds 1-5 showed a weak inhibitory activity against acetylcholinesterase,with the inhibitory rates of 59.4%, 60.0%, 54.6%, 40.0% and 66.6%, respectively. Conclusion A. versicolor BHT-72, a fungus strain from saline-alkali soil in the Yellow River Delta, could produce a variety of active secondary metabolites. Compounds 1 and 2 showed cytotoxic activities against nasopharyngeal carcinoma cell CNE-2, non-small cell lung cancer H1299 and H520, and compounds 1-5 had certain acetylcholinesterase inhibitory activity.

关 键 词：黄河三角洲 杂色曲霉 次级代谢产物 细胞毒活性 乙酰胆碱酯酶抑制活性 

分 类 号：R931.77[医药卫生—生药学]