2株深海来源真菌次级代谢产物的研究
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摘要
目的对2株深海来源真菌Graphostroma sp. MCCC 3A00421和Aspergillus sp. MCCC 3A400414进行化学成分和生物活性研究。方法采用溶剂萃取、柱色谱层析及半制备HPLC等方法对2株深海真菌的发酵产物进行化学分离,通过理化性质及波谱学方法并参阅文献进行化合物结构鉴定,并初步评价其细胞毒活性。结果从菌株3A00421的发酵产物中分离得到了4个化合物,经鉴定其结构分别为3,5-dimethyl-8-methoxy-3,4-dihydroisocoumarin(1)、6-O-methylreticulol(2)、nectriapyrone(3)、demethyl nectriapyrone A(4);从菌株3A00414中分离得到了5个化合物,经鉴定其结构分别为(22E,24R)-麦角甾-5,7,22-三烯-3β-醇(5)、WIN 64821(6)、diorcinol(7)、9-十八碳烯酸(8)、9,12-十八碳二烯酸(9)。其中化合物6具有中等强度的细胞毒活性,其IC_(50)为7.14～15.78μmol/L。结论深海真菌是重要的活性物质来源和生物资源,本研究首次从深海来源Graphostroma属真菌的代谢产物中发现了2个异香豆素和2个苯并吡喃酮类化合物。
Objective To study the chemical constituents and biological activities of two deep-sea-derived fungi,Graphostromasp.MCCC 3A00421 and Aspergillus sp.MCCC 3A00414.Methods The metabolites of two fungi were purified by solvent extraction,column chromatography and semi-preparative HPLC.The structures were established by physicochemical properties,spectral analysis,and comparison with the data of literatures.The proliferation inhibition activities were evaluated by MTT method.Results Four compounds were isolated from the EtOAc extract of the strain 3A00421 and identified as 3,5-dimethyl-8-methoxy-3,4-dihydroisocoumarin(1),6-O-methylreticulol(2),nectriapyrone(3),demethyl nectriapyrone A(4);and five compounds were isolated from 3 A00414:(22E,24R)-ergosta-5,7,22-trien-3β-ol(5),WIN 64821(6),diorcinol(7),9-octadecenoic acid(8),9,12-octadecadienoic acid(9).Compound 6 showed weak cytotoxic activities with IC_(50) ranging from 7.14 to 15.78μmol/L.Conclusion Deep-sea-derived fungi were important microbial resources of bioactive constituents.To date,this was the first discovery of two isocoumarins and two benzopyrones from the metabolites of Graphostromasp.from deep sea.
Objective To study the chemical constituents and biological activities of two deep-sea-derived fungi,Graphostromasp.MCCC 3A00421 and Aspergillus sp.MCCC 3A00414.Methods The metabolites of two fungi were purified by solvent extraction,column chromatography and semi-preparative HPLC.The structures were established by physicochemical properties,spectral analysis,and comparison with the data of literatures.The proliferation inhibition activities were evaluated by MTT method.Results Four compounds were isolated from the EtOAc extract of the strain 3A00421 and identified as 3,5-dimethyl-8-methoxy-3,4-dihydroisocoumarin(1),6-O-methylreticulol(2),nectriapyrone(3),demethyl nectriapyrone A(4);and five compounds were isolated from 3 A00414:(22E,24R)-ergosta-5,7,22-trien-3β-ol(5),WIN 64821(6),diorcinol(7),9-octadecenoic acid(8),9,12-octadecadienoic acid(9).Compound 6 showed weak cytotoxic activities with IC_(50) ranging from 7.14 to 15.78μmol/L.Conclusion Deep-sea-derived fungi were important microbial resources of bioactive constituents.To date,this was the first discovery of two isocoumarins and two benzopyrones from the metabolites of Graphostromasp.from deep sea.
引文
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[2]Bhatnagar I,Kim S K.Immense essence of excellence:marine microbial bioactive compounds[J].Mar Drugs,2010,8(10):2673-2701.
[3]Xiong Z Q,Wang J F,Hao Y Y,et al.Recent advances in the discovery and development of marine microbial natural products[J].Mar Drugs,2013,11(3):700-717.
[4]Leary D,Vierros M,Hamon G,et al.Marine genetic resources:a review of scientific and commercial interest[J].Mar Policy,2009,33(2):183-194.
[5]Thornburg C C,Zabriskie T M,McPhail K L.Deep-sea hydrothermal vents:potential hot spots for natural products discovery[J].J Nat Prod,2010,73(3):489-499.
[6]Fredimoses M,Zhou X,Lin X,et al.New prenylxanthones from the deep-sea derived fungus Emericella sp.SCSIO05240[J].Mar Drugs,2014,12(6):3190-3202.
[7]Li Y,Ye D,Shao Z,et al.A sterol and spiroditerpenoids from a Penicillium sp.isolated from a deep-sea sediment sample[J].Mar Drugs,2012,10(2):497-508.
[8]宋双,许佳怡.海洋来源的曲霉属真菌次级代谢产物及其活性研究进展[J].中山大学研究生学刊(自然科学与医学版),2015(3):20-32.
[9]Sanchez J F,Somoza A D,Keller N P,et al.Advances in Aspergillus secondary metabolite research in the post-genomic era[J].Nat Prod Rep,2012,29(3):351-371.
[10]Tang M,Shen D,Hu Y,et al.Cytotoxic triterpenoid saponins from Symplocos chinensis[J].J Nat Prod,2004,67(12):1969-1974.
[11]宋龙,吕律,王远红,等.罗氏海盘车(Asterias rollestoni)中2种生物碱的分离纯化及其抗肿瘤活性研究[J].中国海洋药物,2016,35(1):50-54.
[12]Kokubun T,Veitch N C,Bridge P D,et al.Dihydroisocoumarins and a tetralone from Cytospora eucalypticola[J].Phytochemistry,2003,62(5):779-782.
[13]Saeed A,Ehsan S.An efficient synthesis of8-hydroxy-6,7-dimethoxy-3-methylisocoumarin(6-O-methylreticulol)[J].Chem Heterocycl Compd,2005,41(11):1381-1385.
[14]Geiseler O,Podlech J.Total synthesis of infectopyrone,aplysiopsenes A-C,ent-aplysiopsene D,phomapyrones Aand D,8,9-dehydroxylarone,and nectriapyrone[J].Tetrahedron,2012,68(36):7280-7287.
[15]Abrell L M,Cheng X C,Crews P.New nectriapyrones by salt water culture of a fungus separated from an Indo-Pacific sponge[J].Tetrahedron Lett,1994,35(49):9159-9160.
[16]Shirane N,Takenaka H,Uena K,et al.Sterol analysis of DMI-resistant and sensitive strains of Venturia inaequalis[J].Phytochemistry,1996,41(5):1301-1308.
[17]Barrow C J,Cai P,Snyder J K,et al.WIN 64821,a new competitive antagonist to substance P,isolated from an Aspergillus species:structure determination and solution conformation[J].J Org Chem,1993,58(22):6016-6021.
[18]Fremlin L J,Piggott A M,Lacey E,et al.Cottoquinazoline A and cotteslosins A and B,metabolites from an Australian marine-derived strain of Aspergillus versicolor[J].J Nat Prod,2009,72(4):666-670.
[19]高长松,钟惠民,曹俊伟,等.海洋真菌zp6次级代谢产物及其抗真菌活性研究[J].中国海洋药物,2012,31(3):7-10.
[20]李宁,匡岩巍,陈明友,等.鼠妇乙醇提取物镇痛抗炎作用及化学成分研究[J].中国实验方剂学杂志,2008,14(11):74-76.
[21]张鹏,包海鹰,图力古尔.珊瑚状猴头菌子实体化学成分研究(Ⅰ)[J].中草药,2012,43(12):2356-2360.