海绵共附生疣孢菌FIM06031细胞毒活性代谢产物的研究

利用正相硅胶、葡聚糖凝胶Sephadex LH-20和反相C18柱层析等方法,从海绵共附生疣孢菌FIM06031的发酵菌丝体提取液中分离到三个化合物(1～3)。通过波谱方法鉴定其中一个化合物harrucomicin C(1)为新倍半萜,另外两个已知化合物为cyperusol C(2)和Nb-乙酰色胺(3)。活性研究表明harrucomicin C对肿瘤细胞株HepG2、EC109和HeLa具显著增殖抑制活性,其IC50值分别为16.99、25.33μM和34.64μM;cyperusol C对肿瘤细胞HeLa和HepG2增殖抑制作用的IC50值分别为149.99μM和167.78μM。     

一株无花果内生真菌及其次生代谢产物

从无花果Ficus carica 叶中分离获得1株具有抗菌活性的内生真菌ZJWCF255,通过形态学和ITS rDNA序列分析将菌种鉴定为炭角菌属Xylaria sp.,其发酵液经活性跟踪分离,采用硅胶柱层析及HPLC等方法获得4个化合物。根据波谱数据,化合物1–4分别鉴定为cytochalasin C、D、Q、R。Cytochalasin Q（3）对11种植物病原真菌均具有较强的抑制活性,对蔓枯病菌的抑制率最强,EC50值为0.04μg/mL。该化合物对3种肿瘤细胞SMMC-772、MCF-7、MGC80-3具有较强体外抑制活性,其IC50值分别为（17.24±2.55）、（7.75±1.37）、（10.30±1.34）μg/mL。首次报道了cytochalasin Q（3）的抗菌活性及对3种肿瘤细胞的体外抑制活性,植物内生真菌是获得抗菌与抗肿瘤活性先导化合物的重要来源。     

灵芝菌丝体中一个三萜类化合物的核磁归属及活性初探

通过液体振荡-静置两阶段发酵获得灵芝菌丝体,并采用硅胶柱色谱层析、反相柱层析和甲醇重结晶的方法,从中分离得到4个三萜类化合物。根据NMR、MS等波谱数据分析,化合物分别被鉴定为lanosta-7,9(11),24-trien-3α-acetoxy-26-oic acid（1）、灵芝酸R（2）、灵芝酸T（3）和灵芝酸S（4）,其中化合物1的核磁信号全归属为首次报道。4个三萜类化合物均具有较好的抑制肿瘤细胞L1210及K562增殖的活性,且化合物1的体外抗肿瘤活性为首次证实,其对肿瘤细胞L1210及K562增殖的半数抑制浓度IC₅₀分别为22.17μmol/L和54.79μmol/L。     

朴树内生镰刀菌HU0174抗真菌次生代谢产物研究

通过硅胶柱层析、大孔吸附树脂柱层析和高效液相制备等色谱技术从一株朴树内生镰刀菌Fusarium sp.HU0174的大米发酵物中分离得到一个新的环酯肽:acuminatum D(1)和6个已知化合物:acuminatums A～C(2～4)、白僵菌素(5)、白僵菌酮(6)和吲哚-3-羧酸(7),运用NMR和MS等谱学方法鉴定了它们的化学结构。采用滤纸片琼脂扩散法测试表明环酯肽类化合物1～4对柑橘绿霉和新月弯孢霉两株植物致病真菌具有明显的体外抑制活性,初步阐明了镰刀菌HU0174的抗真菌活性物质基础。     

彝药鬼吹箫的化学成分研究

采用凝胶树脂(Toyopearl HW-40c)、正相硅胶、反相硅胶(ODS)、大孔树脂(MCI)等柱层析方法从忍冬科鬼吹箫属植物鬼吹箫(Leycesteria formosa Wall.)的茎干部位分离得到8个化合物,包括1个降木脂素类(1)、2个黄酮类(4和5)、3个咖啡酸类(2、3和8)和2个三萜类(6和7)。运用波谱光谱学方法分别鉴定为:samwirin(1)、顺式咖啡酸(2)、反式咖啡酸(3)、木犀草素(4)、芹菜素(5)、3-羟基齐墩果烷(6)、熊果酸(7)和咖啡酸甲脂(8)。化合物1、2、4和5均首次从该植物中分离得到。采用MTT法测试了化合物1对肺癌细胞株(A549)和肝癌细胞株(Hep G2)2种人肿瘤细胞株的体外细胞毒活性,结果表明化合物1在40μM浓度下对所测试的2种细胞株未显示细胞毒活性。     

中药五灵脂的化学成分研究

从中药五灵脂(Trogopterus xanthipes)的丙酮提取物中分离得到3个化合物,其结构经波谱鉴定为3-hy-droxy-(3-hydroxyphenyl)-benzenepropanol(1)、trans-2-(3,5-dihydroxybenzyl)-3-(3-hydroxybenzyl)-γ-butyrolactone(2)和tocopherylquinone(3)。其中化合物1为一个新的降木脂素类成分,化合物2为首次从自然界获得的新化合物,化合物3为首次从该中药中分离得到。化合物3在白血病肿瘤细胞株活性测定实验中显示中等的细胞毒活性,其IC50为20.7μM。     

内生条纹拟盘多毛孢发酵液中细胞毒活性成分研究

从条纹拟盘多毛孢Pestalotopsis virgatula发酵液中分离得到8个化合物,其结构分别被鉴定为：2-(1-甲氧基-1-H-吲哚-3-基)乙醇 (1),2-(1-甲氧基-1-H-吲哚-3-基)乙酸 (2),3β-羟基-5α,8α-过氧化麦角甾-6,22-二烯 (3),麦角甾-4,6,8(14),22-四烯-3-酮 (4),对羟基苯乙醇 (5),邻苯二甲酸二异丁酯 (6),(E)-3-(4-羟基-3-甲氧苯基)败脂酸 (7) 和丁二酸 (8),化合物1–8均为首次从该菌种中分离得到。利用MTT法测试了化合物1 和2对5种人体肿瘤细胞的细胞毒活性,结果显示化合物1和2对5株肿瘤细胞株均具有一定选择性抑制活性。     

漳江口红树林沉积物真菌多样性分析及抗茶叶致病真菌生物活性筛选

以福建漳江口红树林国家级自然保护区红树林沉积物分离的真菌为对象,研究红树林沉积物真菌的多样性和筛选抗茶叶病原真菌活性的菌株。将分离纯化的135株真菌通过形态学和Ribosomal DNA-Internal Transcribed Spacer(rDNAITS)序列测定进行鉴定及多样性分析,归为40个种类型,分别属于17个属,其中青霉属(25%)为优势菌,木霉属(15%)、曲霉属(10%)和镰刀属(10%)次之,表明红树林沉积物真菌具有丰富的多样性;利用平板对峙法对真菌的发酵粗提物抗茶叶病原真菌生物活性研究,结果发现,共有17株(占42.5%)真菌具有抗茶叶病原真菌活性,其中15株能够抑制茶叶轮斑病(Pestalotiopsis theae)LH13,12株能够抑制茶叶炭疽病(Colletotrichum gloeosporioides)LH30,8株能够抑制茶叶溃疡病(Neofusicoccumsp.)LH107,有两株对这三种茶叶致病菌均有较强活性。这些活性菌株分布在6个属中,分别是青霉属(7株)、木霉属(3株)、镰孢属(2株)、枝孢属(2株)、白地霉属(2株)和球腔菌属(1株)。由此可见,红树林沉积物真菌抗菌活性菌株的种属分布具有多样性。     

毛果鱼藤化学成分及生物活性研究

为了解毛果鱼藤(Derris eriocarpa How)藤茎和根中的生物活性成分,采用柱色谱技术,从其乙酸乙酯萃取部位分离得到6个化合物,分别鉴定为:高丽槐素(1)、美迪紫檀素(2)、大黄素(3)、松脂醇(4)、(6R,9R)9-hydroxy-4-megastigmen-3-one(5)、2-methoxygliricidol(6)。这些化合物均为首次从该植物中分离得到。体外抑菌、细胞毒抑制活性测试结果表明,化合物1、2对部分肿瘤细胞株及结核分枝杆菌(H37Rv)有明显抑制活性。     

北极真菌Eutypella sp.D-1中海松烷二萜类化合物的研究

采用硅胶柱、反相硅胶柱和凝胶柱等色谱技术,从北极真菌Eutypella sp.的菌体发酵液提取物中分离纯化得到2个化合物,通过1H和13C NMR、2D NMR等分析方法,并比较相关文献,鉴定这两个化合物为libertellenone C(1)和libertellenone A(2)。测试了化合物1和2对各种癌细胞株的细胞毒活性,其中化合物1对胰腺癌SW1990和胶质瘤U251有一定的细胞毒活性,此外化合物2对稻瘟霉有抑制活性。     

Novel selective PPARdelta agonists: optimization of activity by modification of alkynylallylic moiety

Y-shaped molecules bearing alkynylallylic moieties were found to be potent and selective PPARdelta activators. The alkynylallylic moiety was synthesized from alkyn-1-ols by hydroalumination followed by a cross-coupling reaction. Series of active compounds 6 were obtained by stepwise changing the structure of the known PPARpan agonist 5 into Y-shaped compounds. The most active and selective compound, 6f, had a PPARdelta potency of 0.13 microM, which is 50-fold more potent than compound 5.     

具有纤溶活性作用的海洋真菌代谢产物的分离与菌株鉴定

本文旨在分离具有纤溶活性作用的化合物和鉴定产生纤溶活性化合物的菌株FG216的种属分类。以马铃薯蔗糖培养基为种子培养基,改良查氏培养基为发酵培养基对菌株进行发酵培养,用甲醇作为提取溶剂,通过半制备型高效液相色谱从真菌FG216的1 L发酵液中分离和精制了12 mg纤溶活性化合物,该纤溶活性化合物在纤溶酶原和单链尿激酶性纤溶酶原激活剂相互活化反应体系中添加10μg/mL活性最高。对FG216菌株rDNA的ITS基因(ITS-5.8 S rDNA)进行PCR扩增、测序,从GenBank获取相似序列,通过序列比对分析和系统发育分析表明菌株FG216与Stachybotrys longispora同源性最高。从分离的海洋微生物葡萄穗霉属菌株FG216分离得到的纤溶活性化合物具体促进纤溶酶原和单链尿激酶性纤溶酶原激活剂相互活化的作用。     

NMR analysis of tautomerisms of active pinacidil-type potassium channel openers and a less active one

In order to clarify the structural difference between active pinacidil-type potassium channel openers and a less active one, the tautomerisms of pinacidil derivatives 1-3 were investigated by NMR spectrometries. The predominant tautomer of the less active compound 3 was different from those of the active compounds 1 and 2.     

A new benzoangelicin with strong photobiological activity

Benzoangelicins 4-6 were synthesized in good yields from 7-hydroxy-5-methoxy-4-methylcoumarin (1). In the absence of UVA radiation, compounds 5 and 6 were only weakly active against HL60 and HeLa tumour cells; in its presence, compound 6 was 10 times more active than the reference compound 8-methoxypsoralen. None of 4-6 exhibited cutaneous phototoxicity.     

Purification and characterization of a component produced by Lactobacillus fermentum that inhibits the adhesion of K88 expressing Escherichia coli to porcine ileal mucus

It has previously been shown that Lactobacillus fermentum strain 104r releases compounds into its culture fluid that inhibit the adhesion of enterotoxigenic Escherichia coli K88. The aim of the present study was to purify and identify this compound. Judged by gel filtration, the compound was found to be approximately 1700 kDa. The amount of active compound increased upon prolonged incubation, while the number of viable cells reduced, suggesting that the activity was coming from dead cells. As the activity can be destroyed by lysozyme treatment and contains glucose, N -acetylglucosamine and galactose, it was concluded that cell wall fragments are the active agent, although cell wall preparations did not have the same effect. Adhesion to some mucus fractions could be inhibited by spent culture fluid, indicating specific interaction between mucus and the active compound. The compound was not able to interfere with the adhesion of E. coli 1107 to neutral lipids from mucus which contain a glycolipid receptor for K88 fimbriae.     

Characterization of neutral blood group B-active glycosphingolipids of rat gastric mucosa. A novel type of blood group active glycosphingolipid based on isogloboside

The blood group active glycosphingolipids of rat gastric mucosa have been investigated. Only blood group B active structures were found, two of which have been structurally characterized by monoclonal antibodies, mass spectrometry, permethylation analyses, proton NMR spectroscopy, and exoglycosidase digestions. A six-sugar compound based on a gangliotetraosylceramide core was isolated and shown to have the following structure: (Formula: see text). The same compound was recently isolated from rat bone marrow cells and characterized by Taki et al. (Taki, T., Kimura, H., Gasa, S., Nakamura, M., and Matsumoto, M. (1985) J. Biol. Chem. 260, 6219-6225). The possible precursor compounds of this structure, gangliotriaosylceramide and gangliotetraosylceramide, were also found in the gastric mucosa. A seven sugar compound, based on isogloboside, was isolated from the gastric mucosa and shown to have the following structure: (formula; see text) The latter compound is novel and extends the list of different types of core structures found for blood group glycolipids. The epithelial cells of the stomach are unique among the cells lining the gastrointestinal tract in having blood group active glycolipids based on ganglio- and isogloboseries core structures.     

Gibberellin-like substances in peach tissue: Separation by thin-layer electrophoresis and chromatography

Summary Thin-layer electrophoresis in conjunction with thin-layer chromatography proved an excellent method for separating gibberellin-like compounds extracted from small quantities of peach tissue. Eleven compounds active in the barley-endosperm gibberellin bioassay were separated from peach shoot tips. Two of these were possibly identical with known gibberellins but the remainder were distinctly different. Of the latter, five were acidic, one was neutral, and three were basic. The most active compound in shoot tips may have been GA₁ or GA₃ but in seeds the most active compound resembled no known gibberellin.     

Antimicrobial activity of xanthatin from Xanthium spinosum L.

Dichloromethane extracts from Xanthium spinosum L. were fractionated and the fractions tested for their bactericidal and fungicidal activity. From the active fraction, a compound was isolated and identified as xanthatin (I). Xanthatin was active against Colletotrichum gloesporoides, Trichothecium roseum, Bacillus cereus and Staphylococcus aureus.     

一种被毛孢(Hirsutella sp.)培养液中自由基清除剂的分析、分离和制备

[目的]在一次对虫生真菌代谢物进行大规模的清除自由基活性物质筛选中,发现一种被毛孢(Hirsutella sp.)菌株RCEF0881发酵液中存在有较强的清除自由基活性物质.本研究目的是初步搞清这些活性成分的具体组成,并制备出一定量的纯品用于进一步的结构鉴定.[方法]用有机溶剂法提取活性成分;用二苯基苦基苯肼自由基(DPPH)酶标仪法和薄层色谱法进行活性测定;用高分辨液质联用方法进行活性成分初步分析和鉴定;用反相制备色谱法制备活性组分.[结果]提取实验结果表明具清除自由基活性的物质能较好地被乙酸乙酯提取出来;液相色谱-质谱-活性测定分析表明提取物中活性组分的可能分子式分别为C7H6O4、C8H8O3和C12H14N2O.结合色谱特性、紫外光谱特征、质谱碎片和数据库查询可初步推断它们分别为二羟基苯甲酸、羟基甲基苯甲酸和生物碱类物质,但具体结构还有待于进一步确认.从高效液相色谱和质谱离子流的峰面积可知上述3种活性物质中C12H14N2O的含量最高.本研究成功地用反相制备色谱制备出该天然活性组分的纯品.该3种清除自由基活性物质都是首次发现存在于虫生真菌的代谢物中.     

一种被毛孢菌丝体中抗肿瘤活性组分的分离纯化和液质联用分析

在一次多菌株的生物活性测定中,发现一株被毛孢菌株RCEF0851菌丝体提取物具有较强的抗肿瘤CHO细胞的活性。本研究用不同溶剂对活性组分进行了提取试验,发现乙酸乙酯能最大程度地提取出该活性成分。分离试验表明该提取物较适于用反相柱Synergi Hydro进行分离。活性指导下的分离得到一活性组分的纯品Hh-1。该组分在40μg/mL时对CHO细胞的抑制率达到83.61%。高分辨质谱分析表明该活性化合物的可能分子式是C30H22O10。该分子为首次从虫生真菌中发现。