黄芪内生真菌AR15中吲哚二酮哌嗪及其对黄芪白粉病原菌的抑制作用
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摘要
为了研究黄芪内生真菌AR15的次级代谢产物的结构及其对黄芪白粉病原菌的抑制作用。采用形态学方法和ITS序列鉴定该AR15,使用反复硅胶柱色谱法、Sephadex LH-20凝胶色谱法,结合HPLC对AR15的发酵产物进行分离纯化,通过波谱分析鉴定其发酵液中分离得到8个化合物的结构。结果表明:黄芪内生真菌AR15为Penicilliumsp.,分离到的8个吲哚二酮哌嗪类生物碱分别鉴定为fumitremorgin B(1)、cyclotryprostatins B(2)、verruculogen(3)、tryprostatin B(4)、tryprostatin A(5)、cyclotryprostatin A(6)、cyclotryprostatins C(7)、cyclotryprostatins D(8),所有吲哚二酮哌嗪对黄芪白粉病原菌都显示出一定的抑制作用,其中化合物1,3和6的MIC值达到3.13、1.56和6.25μg·mL~(-1)。
The chemical constituents from endophytic fungus AR15 of Astragalus membranaceus and antimicrobial activity to Erysiphe pisi were investigated.According to the morphological features,cultural characteristics and ITS sequences,the strains AR15 were indentified as Penicilliumsp.The compounds were isolated by column chromatography,Sephadex LH-20,and HPLC.Eight indole diketopiperazines were obtained and elucidated as fumitremorgin B(1),cyclotryprostatins B(2),verruculogen(3),tryprostatin B(4),tryprostatin A(5),cyclotryprostatin A(6),cyclotryprostatins C(7),and cyclotryprostatins D(8).All indole diketopiperazines showed inhibitory activity to E.pisi,and compound 1,3and 6showed strong inhibitory activity with MIC values of 3.13,1.56 and 6.25μg·mL~(-1),respectively.
The chemical constituents from endophytic fungus AR15 of Astragalus membranaceus and antimicrobial activity to Erysiphe pisi were investigated.According to the morphological features,cultural characteristics and ITS sequences,the strains AR15 were indentified as Penicilliumsp.The compounds were isolated by column chromatography,Sephadex LH-20,and HPLC.Eight indole diketopiperazines were obtained and elucidated as fumitremorgin B(1),cyclotryprostatins B(2),verruculogen(3),tryprostatin B(4),tryprostatin A(5),cyclotryprostatin A(6),cyclotryprostatins C(7),and cyclotryprostatins D(8).All indole diketopiperazines showed inhibitory activity to E.pisi,and compound 1,3and 6showed strong inhibitory activity with MIC values of 3.13,1.56 and 6.25μg·mL~(-1),respectively.
引文
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[2]LI S M.Prenylated indole derivatives from fungi:structure diversity,biological activities,biosynthesis and chemoenzymatic synthesis[J].Nat.Prod.Rep.,2010,27:57-78.
[3]LI X J,ZHANG Q,ZHANG A L,et al.Metabolites from Aspergillus fumigatus,an endophytic fungus associated with Melia azedarach,and their antifungal,antifeedant,and toxic activities[J].J.Agric.Food Chem.,2012,60:3424-3431.
[4]ZHANG Q,WANG S Q,TANG H Y,et al.Potential allelopathic indole diketopiperazines produced by the plant endophytic Aspergillus fumigatus using the one strain-many compounds method[J].J.Agric.Food Chem.,2013,61:11447-11452.
[5]LI H Q,LI X J,WANG Y L,et al.Antifungal metabolites from Chaetomium globosum,an endophytic fungus in Ginkgo biloba[J].Biochem.Syst.Ecol.,2011,39:876-879.
[6]田小曼,陈阿敏.火棘抑菌内生真菌的筛选与拮抗植物病原菌作用研究[J].西北林学院学报,2012,27(5):117-120.TIAN X M,CHEN A M.Screening of Pyracantha fortuneana endophytic fungus and function examination of antagonism to plant pathogetic fungi[J].Journal of Northwest Forestry University,2012,27(5):117-120.(in Chinese)
[7]王维,马养民,张弘弛,等.黑果枸杞内生真菌E21菌株次生代谢产物的研究[J].中国新药杂志,2013,22(4):460-464.WANG W,MA Y M,ZHANG H C,et al.Metabolites from the strain E21,an endophytic fungus in Lycium ruthenicum[J].Chinese Journal of New Drugs,2013,22(4):460-464.(in Chinese)
[8]屈子睿,马养民,许倩,等.防风内生真菌DL02菌株次生代谢产物的结构与活性[J].西北林学院学报,2015,30(6):1-5.QU Z R,MA Y M,XU Q,et al.Structure and activity of secondary metabolites of endophytic fungus DL02strain in Saposhnikovia divaricate[J].Journal of Northwest Forestry University,2015,30(6):1-5.(in Chinese)
[9]ZHOU F,ZHANG H C,LIU R,et al.Isolation and biological evaluation of secondary metabolites of the endophytic fungus Aspergillus fumigatus from Astragalus membranaceus[J].Chem.Nat.Compd.,2013,49:568-570.
[10]任虹,曹学丽,王巧娥,等.真菌萨氏曲霉D 2-6抗肿瘤活性代谢产物[J].中国药学杂志,2011,46(8):569-575.REN H,CAO X L,WANG Q E,et al.Antitumor metabolites from fungus Aspergillus sydowi D 2-6[J].Chinese Pharmaceutical Journal,2011,46(8):569-575.(in Chinese)
[11]赵文英,张亚鹏,朱天骄,等.海洋来源真菌A-f-11中吲哚二酮哌嗪类抗肿瘤活性成分的研究[J].中国抗生素杂志,2006,31(12):749-752,764.ZHAO W Y,ZHANG Y P,ZHU T J,et al.Studies on the indolyl diketopiperazine analogs produced by marine-derived fungus A-f-11[J].Chinese Journal of Antibiotics,2006,31(12):749-752,764.(in Chinese)
[12]CUI C B,KAKEYA H,OSADA H.Novel mammalian cell cycle inhibitor,cyclotryprostatins A-D,produced by Aspergillus fionigatus,which inhibit mammalian cell cycle at G2/M phase[J].Teterahedron,1997,53(1):59-72.
[13]FAYOS J,LOKENSGARD D,CLARDY J,et al.Structure of verruculogen,a tremor producing peroxide from Penicillium verruculosum[J].J.Am.Chem.Soc.,1974,96:6785-6787.
[14]CUI C B,KAKEYA H,OSADA H.Novel mammalian cell cycle inhibitor,tryprostatins A,B and other Diketopiperazines produced by Aspergillus fumigatus II.physicochemical properties and structures[J].J.Antibiot.,1996,49:534-540.
[15]杨春清,孙明舒,丁万隆.黄芪病虫害种类及为害情况调查[J].中国中药杂志,2004,29(12):1130-1132.YANG C Q,SUN M S,DING W L.Investigation of the diseases and insect pests of Astragalus membranaceus[J].China Journal of Chinese Materia Medica,2004,29(12):1130-1132.(in Chinese)