海洋放线菌Streptomyces sp. HNWSW-49的次生代谢产物研究

对1株具有抗芒果炭疽病菌活性的海口湾海泥来源放线菌Streptomyces sp.HNWSW-49发酵液的化学成分进行研究。采用多种色谱技术对化合物进行分离纯化,以波谱数据确定化合物的结构。从来源于海口湾海泥的放线菌Streptomyces sp.HNWSW-49发酵液的乙酸乙酯提取物中分离鉴定了7个含氮化合物,分别为:环-(苯丙-丙)二肽(1),环-(亮-甘)二肽(2),环-(苯丙-缬)二肽(3),环-(羟脯-苯丙)二肽(4),N-(2-苯基)乙酰胺(5),β-腺苷(6),和2-哌啶酮(7)。所有化合物均为首次从该放线菌中分离得到,其中化合物6为首次从微生物中分离得到。      

蝴蝶和蝗虫肠道共生菌次生代谢产物的分离

对分离自健康蝴蝶和蝗虫肠道的共生菌Aspergillus sp. HDf1,Aspergillus sp. HCf2和Amycolatopsis sp. HCa1发酵液的化学成分进行了研究。采用色谱技术对化合物进行分离纯化,以波谱技术确定化合物的结构,结果从蝴蝶肠道共生真菌Aspergillus sp. HDf1,蝗虫肠道共生真菌Aspergillus sp. HCf2和放线菌Amycolatopsis sp. HCa1发酵液的乙酸乙酯提取物中各分离鉴定了1个化合物,分别为N-benzoylphenylalanyl-L-phenylalaninol acetate（1）,bostrycin（2）和2-spirocyclohexyl-2,3-dihydroquinazolin-4（1H）-one（3）;以上化合物均为首次从昆虫来源的共生菌中分离得到,其中化合物3是首次从Amycolatopsis属放线菌中发现。     

海洋共生菌Aspergillus sp.HDf2新活性次生代谢产物研究(英文)

对紫海胆共生真菌Aspergillus sp.HDf2的次生代谢产物进行分离和鉴定。采用摇瓶液体发酵,运用柱层析等方法对其发酵液成分进行分离纯化,经波谱解析和质谱分析进行结构鉴定,并运用滤纸片法对化合物进行体外抗金黄色葡萄球菌的活性测试。结果从该真菌发酵产物中鉴定出2个secospiculisporic acid新类似物,分别为secospiculisporic acid B(1)和secospiculisporic acid C(2),其中化合物1具有弱抗菌活性,抑菌直径为9.2 mm(20 mg/mL)。首次对化合物1的NMR数据进行了归属,化合物2为secospiculisporic acid类的新化合物。     

Secondary Metabolites Produced by a Cockchafer-derived Streptomyces sp. BCa1

对一株分离自昆虫铜绿金龟子幼虫肠道的链霉菌Streptomyces sp. BCa1的次生代谢产物进行化学研究。采用摇瓶发酵，并用柱色谱技术对该链霉菌的次生代谢产物进行分离纯化和利用光谱分析进行结构鉴定。结果从菌株Streptomyces sp. BCa1的发酵液中分离获得1个具有Hsp90蛋白抑制活性的格尔德霉素（geldanamycin）以及2个萘醌型大环内酯类化合物。所有化合物均为首次从昆虫来源的链霉菌中发现，且格尔德霉素为其主要产物，表明昆虫来源的放线菌具有良好的开发前景。     

铜绿金龟子肠道链霉菌Streptomyces sp. BCa1 菌体的抗菌成分研究

为从昆虫来源的放线菌次级代谢产物中寻找药物先导分子，对铜绿金龟子幼虫肠道链霉菌Streptomyces sp. BCa1菌丝体化学成分进行了研究。通过活性跟踪，从其菌丝体的氯仿甲醇萃取物中分离得到主要成分1。利用高分辨质谱、一维和二维核磁波谱技术，将该主要成分1鉴定为具有双重旋转对称结构的不饱和大环内酯类抗生素阿扎霉素（elaiophylin），具有显著的抗金黄色葡萄球菌活性。该类化合物为首次从昆虫来源的放线菌中发现。     

鹦歌岭土壤来源Streptomyces sp. YG-7的次生代谢产物及其α-葡萄糖苷酶抑制活性研究

为了研究原始热带雨林鹦歌岭土壤放线菌（Streptomyces sp.）YG-7的次生代谢产物及其α-葡萄糖苷酶抑制活性,采用多种柱色谱方法对土壤放线菌YG-7的发酵产物进行分离纯化得到9个化合物,经过波谱数据分析分别鉴定为：(1) 2-acetamido-5-chlorobenzamide, (2) cyclo (L-Pro-L-Leu), (3) 3,6-dibenzylidene-2,5-piperazinedione, (4) albonoursin, (5) (3Z,6S)-3-benzylidene-6-isobutylpiperazine-2,5-dione, (6) 3-hydroxy-2-methyl-4-pyrone, (7) isophthalic acid, (8) methyl 3-carbamoylbenzoate, (9) 2,3-dihydroxypropyl hexadecanoate. 其中,化合物1、7和8为新天然产物。活性测试结果表明化合物1、3~5和7~8对α-葡萄糖苷酶具有明显的抑制活性。     

冰菜乙醇提取物乙酸乙酯和正丁醇相的化学成分分离鉴定

本研究以冰菜（Mesembryanthemum crystallinum L.）为实验材料,运用多种柱色谱和波谱技术,从冰菜乙醇提取物的乙酸乙酯和正丁醇相中共分离鉴定得到了11个单体化合物,其中苯丙素类化合物2个,分别是顺式对羟基肉桂酸（化合物4）、阿魏酸（化合物3）;生物碱类化合物2个,分别是烟酸（化合物6）、ethane-1,2-diyldinicotinate（化合物7）;糖苷类化合物5个,分别是2-ethoxy-5-(hydroxymethyl)tetrahydrofuran-3,4-diol（化合物5）、3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl(E)-3-(4-hydroxy-3-methoxyphenyl)acrylate（化合物8）、(E)-2-(hydroxymethyl)-6-(4-(3-hydroxyprop-1-en-1-yl)-2-methoxyphenoxy)tetrahydro-2H-pyran-3,4,5-triol（化合物9）、6-(1R,2S-2-hydroxy-4-(S,E-3-hydroxybut-1-en-1-yl)-3,5,5-trimethylcyclohex-3-en-1-yl)oxy-5-(hydroxymethyl)tetrahydro-2H-pyran-2,3,4-triol（化合物10）、E-4-hydroxy-3,5,5-trimethyl-4-(3-((3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)but-1-en-1-yl)cyclohex-2-en-1-one（化合物11）;苯丙呋喃酮类化合物1个:黑麦草内酯（化合物2）;甾体类化合物1个:β-谷甾醇（化合物1）。本研究丰富了冰菜中的化学成分,也为更好地开发利用冰菜的功能性成分提供理论依据,有利于冰菜的推广种植。     

基于SBSE-GC-MS的紫芽茶挥发性成分分析

采用搅拌棒吸附萃取(SBSE)技术结合气相色谱质谱联用(GC-MS)分析了6个代表性紫芽茶中的挥发性成分。结果表明,紫芽茶中具有丰富的挥发性成分,化合物种类和数目高于对照绿茶;芳樟醇、香叶醇、α-松油醇、α-紫罗酮、β-紫罗酮、(E, E)-2, 4-庚二烯醛、水杨酸甲酯、邻甲氨基苯甲酸甲酯、二氢猕猴桃内酯和对乙酰氨基苯酚等化合物是紫芽茶中含量最丰富的香气成分。相对气味活性值(ROAV)分析表明,β-大马士酮、β-紫罗酮、反式-2,4-癸二烯醛、2-己烯醛、α-紫罗酮和芳樟醇等6种香气成分可能是紫芽茶中一些关键的致香成分;另外,1-辛烯-3-醇、二氢猕猴桃内酯、正己醛、正癸醛、β-环高柠檬醛、反式-2-壬醛、正庚醛、β-环柠檬醛和正辛醛等9种成分可能对紫芽茶的整体香气具有重要的修饰作用。     

沉香样品中曲霉属真菌菌株 HNWSW-20 的分离鉴定及其次生代谢产物的研究

本文采用平板分离法从沉香样品中分离得到一株真菌 HNWSW-20,从形态学和分子生物学上鉴定其为曲霉菌（Aspergillus sp.）,并利用多种色谱技术对其次生代谢产物进行分离纯化,根据波谱数据和理化性质鉴定其化合物结构为：2?,3?-dihydrosorbicillin（1）,sorbicillin（2）,2,3-二氢-2-(1-丙烯)-6,8-二甲基-7-羟基-色酮（3）,邻苯二甲酸二丁酯（4）,7-羟基-异苯并呋喃-1(3H)-酮（5）二十烷酸甲酯（6）;分别采用 Ellman 比色法和 pNPG 法测定化合物的乙酰胆碱酯酶抑制活性和 α-葡萄糖苷酶抑制活性,结果显示上述化合物 1、2、4 具有乙酰胆碱酯酶抑制活性,而化合物 1、3、5 具有 α-葡萄糖苷酶抑制活性。本文中化合物 1~2 为首次从曲霉属中分离得到,并首次报道具有乙酰胆碱酯酶和 α-葡萄糖苷酶抑制活性。     

海南粗榧内生真菌F127发酵液的次级代谢产物研究

对海南粗榧(Cephalotaxus hainanensis Li.)内生真菌F127发酵液化学组分进行研究。用多种色谱技术对F127代谢产物进行分离纯化,以LC-MS、ESI-MS和超导核磁共振分析鉴定化合物结构,最后采用MTT法测定化合物的抗肿瘤活性。从海南粗榧内生真菌F127的发酵液中分离得到5个单体化合物,分别鉴定为oblongolide T(1)、sorbicillin(2)、邻苯二甲酸二丁酯(3)、phomopsolide B(4)、6,8-二羟基-3-甲基-3,4-二氢异香豆素(5),且化合物1、4、5对肿瘤细胞K562、NB4、HL-60、Hep G-2和Lovo表现出不同抑制活性。化合物4对5株肿瘤细胞均表现出抑制活性,对K562、NB4、HL-60抑制效果显著,IC50值分别为3.35、0.014和0.16μg/m L,对Hep G-2和Lo Vo只有温和抑制作用;化合物1对K562、NB4、HL-60抑制作用良好,IC50值分别为51.82、54.25和29.31μg/m L;化合物5对NB4和Hep G-2则具有一定抑制活性;化合物2和3对测试细胞株未表现出抑制活性。5个化合物均是首次从海南粗榧内生真菌中分离得到,并首次报道了化合物1、4对K562、NB4、HL-60的优良细胞毒活性,为进一步研究海南粗榧内生真菌中的活性天然产物奠定了基础。     

A New Analogue of Echinomycin and a New Cyclic Dipeptide from a Marine-Derived Streptomyces sp. LS298

Quinomycin G (1), a new analogue of echinomycin, together with a new cyclic dipeptide, cyclo-(l-Pro-4-OH-l-Leu) (2), as well as three known antibiotic compounds tirandamycin A (3), tirandamycin B (4) and staurosporine (5), were isolated from Streptomyces sp. LS298 obtained from a marine sponge Gelliodes carnosa. The planar and absolute configurations of compounds 1 and 2 were established by MS, NMR spectral data analysis and Marfey’s method. Furthermore, the differences in NMR data of keto-enol tautomers in tirandamycins were discussed for the first time. Antibacterial and anti-tumor activities of compound 1 were measured against 15 drug-sensitive/resistant strains and 12 tumor cell lines. Compound 1 exhibited moderate antibacterial activities against Staphylococcuse pidermidis, S. aureus, Enterococcus faecium, and E. faecalis with the minimum inhibitory concentration (MIC) values ranged from 16 to 64 μg/mL. Moreover, it displayed remarkable anti-tumor activities; the highest activity was observed against the Jurkat cell line (human T-cell leukemia) with an IC₅₀ value of 0.414 μM.     

麦冬须根正丁醇萃取物化学成分的分离与鉴定

为了研究麦冬须根中的化学成分,本研究采用大孔吸附树脂、ODS和Sephadex LH-20多种柱色谱技术对麦冬须根乙醇提取物的正丁醇萃取物进行分离纯化;通过波谱数据与理化性质分析并结合文献进行化合物结构鉴定。从麦冬须根的正丁醇萃取物中分离得到10个化合物,其结构分别鉴定为5-甲氧基-6-甲基-7-羟基-8-醛基-3S-(3', 4' -亚甲二氧基苯)-4-二氢色原酮（1）、甲基麦冬黄烷酮A（2）、甲基麦冬黄烷酮B（3）、大黄素（4）、肥牛木素（5）、E-对羟基桂皮酸（6）、Z-对羟基桂皮酸（7）、4-羟基苯甲酸（8）、25R-spirost-5-ene-1β, 3β-diol 1-O-[α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside]（9）和β-谷甾醇（10）。其中化合物1为新的高异黄酮类化合物,命名为麦冬黄烷酮D',化合物5和7为首次从百合科植物中分离得到,化合物9为首次从该植物中分离得到。     

Neuroprotective Effect of Cyclo-(L-Pro-L-Phe) Isolated from the Jellyfish-Derived Fungus Aspergillus flavus

Peroxisome proliferator-activated receptor (PPAR) expression has been implicated in pathological states such as cancer, inflammation, diabetes, and neurodegeneration. We isolated natural PPAR agonists—eight 2,5-diketopiperazines—from the jellyfish-derived fungus Aspergillus flavus. Cyclo-(L-Pro-L-Phe) was the most potent PPAR-γ activator among the eight 2,5-DKPs identified. Cyclo-(L-Pro-L-Phe) activated PPAR-γ in Ac2F rat liver cells and SH-SY5Y human neuroblastoma cells. The neuroprotective effect of this partial PPAR-γ agonist was examined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase release, and the Hoechst 33342 staining assay in SH-SY5Y cells. Our findings revealed that cyclo-(L-Pro-L-Phe) reduced hydrogen peroxide-induced apoptosis as well as the generation of reactive oxygen species. Rhodamine 123 staining and western blotting revealed that cyclo-(L-Pro-L-Phe) prevented the loss of mitochondrial membrane potential and inhibited the activation of mitochondria-related apoptotic proteins, such as caspase 3 and poly (ADP-ribose) polymerase. Moreover, cyclo-(L-Pro-L-Phe) inhibited the activation and translocation of nuclear factor-kappa B. Thus, the partial PPAR-γ agonist cyclo-(L-Pro-L-Phe) demonstrated potential neuroprotective activity against oxidative stress-induced neurodegeneration in SH-SY5Y cells.     

Actinomycetes from sediments in the Trondheim fjord, Norway: diversity and biological activity

The marine environment represents a largely untapped source for isolation of new microorganisms with potential to produce biologically active secondary metabolites. Among such microorganisms, Gram-positive actinomycete bacteria are of special interest, since they are known to produce chemically diverse compounds with a wide range of biological activities. We have set out to isolate and characterize actinomycete bacteria from the sediments in one of the largest Norwegian fjords, the Trondheim fjord, with respect to diversity and antibiotic-producing potential. Approximately 3,200 actinomycete bacteria were isolated using four different agar media from the sediment samples collected at different locations and depths (4.5 to 450 m). Grouping of the isolates first according to the morphology followed by characterization of isolates chosen as group representatives by molecular taxonomy revealed that Micromonospora was the dominating actinomycete genus isolated from the sediments. The deep water sediments contained a higher relative amount of Micromonospora compared to the shallow water samples. Nine percent of the isolates clearly required sea water for normal growth, suggesting that these strains represent obligate marine organisms. Extensive screening of the extracts from all collected isolates for antibacterial and antifungal activities revealed strong antibiotic-producing potential among them. The latter implies that actinomycetes from marine sediments in Norwegian fjords can be potential sources for the discovery of novel anti-infective agents.     

A new diketopiperazine, cyclo-(4-S-hydroxy-R-proline-R-isoleucine), from an Australian specimen of the sponge Stelletta sp

While investigating the cytotoxic activity of the methanol extract of an Australian marine sponge Stelletta sp. (Demospongiae), a new diketopiperazine, cyclo-(4-S-hydroxy-R-proline-R-isoleucine) (1), was isolated together with the known bengamides; A (2), F (3), N (4), Y (5), and bengazoles; Z (6), C(4) (7) and C(6) (8). The isolation and structure elucidation of the diketopiperazine (1), together with the activity of 1-8 against a panel of human and mammalian cell lines are discussed.     

Methylthio-Aspochalasins from a Marine-Derived Fungus Aspergillus sp.

Two novel aspochalasins, 20-β-methylthio-aspochalsin Q (named as aspochalasin V), (1) and aspochalasin W (2), were isolated from culture broth of Aspergillus sp., which was found in the gut of a marine isopod Ligia oceanica. The structures were determined on the basis of NMR and mass spectral data analysis. This is the first report about methylthio-substituted aspochalasin derivatives. Cytotoxicity against the prostate cancer PC3 cell line and HCT116 cell line was assayed using the MTT method. Apochalasin V showed moderate activity at IC₅₀ values of 30.4 and 39.2 μM, respectively.