恒山黄芪内生真菌Penicillium sp.中gliotoxin类代谢产物的分离和生物活性

目的:研究恒山黄芪内生真菌Penicillium sp.的gliotoxin类代谢产物和其对黄芪白粉病原菌Erysiphe pisi.的抑制作用。方法:次生代谢产物的分离纯化采用反复硅胶柱色谱法,Sephadex LH-20凝胶色谱法和HPLC方法,并通过化学方法结合核磁共振分析和质谱鉴定其化学结构,抑菌活性测试方法采用最小抑制浓度法。结果:从恒山黄芪内生真菌Penicillium sp.的固体发酵萃取物中分离得到7个gliotoxin类代谢产物,经波谱分析分别鉴定为gliotoxin(1),bisdethiobis(methylthio)gliotoxin(2),dehydroxybisdethiobis(methylthio)gliotoxin(3),dehydrogliotoxin(4),6-deoxy-5a,6-didehydrogliotoxin(5),didehydrobisdethiobis(methylthio)gliotoxin(6),bis-N-norgliovietin(7),抑菌活性测试结果显示,化合物1,4和5对黄芪白粉病原菌显示出强抑制作用,最小抑菌浓度(MIC)分别达到1.56,0.78,6.25 mg·L-1。结论:所有化合物都是首次从黄芪内生真菌发酵产物中分离得到,黄芪内生真菌Penicillium sp.可以作为潜在的产生gliotoxin类代谢产物的菌种资源。     

雷公藤内生真菌中的环肽及其乙酰胆碱酯酶抑制活性

目的:内生菌作为一种良好的生物资源,已产生许多结构新颖、活性多样的代谢产物,在进行药用植物内生菌的研究中,分离得到了一株踝节菌属真菌,该属真菌是一个产多样代谢产物的真菌,从该内生菌中分离鉴定环肽类成分,并研究其乙酰胆碱酯酶抑制活性。方法:利用柱色谱法,包括硅胶柱色谱、大孔树脂柱色谱和小孔树脂(MCI)凝胶柱色谱等分离化合物;利用波谱方法,包括氢核磁共振、碳核磁共振、电喷雾质谱等鉴定化合物结构;采用改良的Ellman法测定化合物的乙酰胆碱酯酶抑制活性。结果:分离鉴定了4个环肽,它们分别鉴定为discarine-M(1), fumitremorgin C(2),fructigenine B(3), spirotryprostatin A(4),化合物1显示了中等强度的抗乙酰胆碱酯酶活性,其半抑制浓度(IC₅₀) 56 μmol·L^-1。结论:分离的4个化合物均为从踝节菌属(Talaromyces)真菌中首次分得。     

太子参内生真菌草酸青霉中1个新的香豆酮类化合物

目的 研究太子参Pseudostellaria heterophylla内生真菌草酸青霉Penicillium oxalicum的次级代谢产物。方法 采用正、反相硅胶柱色谱，葡聚糖凝胶Sephadex LH-20柱色谱以及制备薄层色谱（pTLC）等色谱技术进行系统分离纯化，采用质谱（MS）、核磁共振（NMR）等波谱学手段对单体化合物进行结构鉴定。结果 从草酸青霉发酵产物的醋酸乙酯萃取液中分离鉴定了12个化合物，包括1个香豆酮类化合物5，7-二羟基-2-甲基苯并呋喃-3-羧酸（1）、5个异香豆素类化合物（3R，4R）-（-）-4-hydroxymellein（2）、O-methylmellein（3）、acremonone G（4）、decarboxycitrinone（5）和decarboxyhydroxycitrinone（6），4个没药烷型倍半萜类化合物（7S，11S）-（+）-12-acetoxysydonic acid（7）、（S）-（+）-11-dehydrosydonic acid（8）、sydonic acid（9）和1-hydroxy-boivinianin A（10），2个混源萜类化合物decaturin D（11）和decaturin C（12）。结论 化合物1为新化合物，命名为草酸苯并呋喃酸A，化合物2～6、10为首次从草酸青霉中分离得到。     

人参内生真菌Aspergillus terreus RSB2007的次生代谢产物的研究

目的 研究人参内生真菌Aspergillus terreus RSB2007次生代谢产物的化学成分,以期发现新的化合物。方法 该菌大米固体发酵的醋酸乙酯提取物经硅胶、Sephadex LH-20及HPLC等多种色谱技术进行分离纯化,并根据核磁共振谱、质谱、圆二色谱（electronic circular dichroism,ECD）以及计算ECD等方法鉴定化合物的结构。结果 从人参内生真菌Aspergillus terreus RSB2007发酵产物中初步分离鉴定了4个化合物,分别鉴定为7,8''-二羟基-3,4,6-三甲基-7''-苯基-1,3,4,7''-四氢-2H-吡喃并[2,3,4-de]色烯-8''-羧酸盐（1）、butyrolactone II（2）、aspernolide A（3）和versicolactone B（4）。结论 化合物1为新的聚酮类化合物,命名为曲霉酮A。     

黑面神根部化学成分的研究

目的 研究山漆茎属植物黑面神Breynia fruticosa根的化学成分。方法 利用硅胶柱色谱和Sephadex LH-20等色谱方法进行分离纯化,应用NMR等方法鉴定结构。结果 从黑面神根95%乙醇冷浸液的醋酸乙酯部位分离鉴定了13个化合物,其中包括4个三萜类化合物：无羁萜（1）、木栓醇（2）、羽扇烯酮（3）和算盘子二醇（4）;3个甾醇类化合物：β-谷甾醇（5）、豆甾烷-3β, 6β-二醇（6）和β-sitosterylglucoside-6′-octadecanoate（7）;2个脑苷类化合物：1-O-β-D-glucopyranosyl-(2S, 3R, 4E, 8Z)-2-[(2-hydroxyoctadecanoyl) amido]-4, 8-octadecadiene-1, 3-diol（8）和1-O-β-D-glucopyranosyl-(2S, 3S, 4R, 8Z)- 2-[(2R)-2-hydroxypentacosanoylamino]-8-octadecene-1, 3, 4-triol（9）;4个其他类化合物：(?)-表儿茶素（10）、ε-己内酯（11）、aviculin（12）和香草醛（13）。结论 化合物3、4、6～9和11为首次从山漆茎属植物中分离得到,其中化合物11为首次从天然产物中分离得到。     

海洋真菌链孢粘帚菌（Gliocladium catenulatum T31）抗肿瘤活性代谢产物

 目的 阐明海洋真菌链孢粘帚菌（Gliocladium catenulatum T31）的抗肿瘤活性次级代谢产物。方法 摇床发酵培养生产菌T31,活性跟踪分离纯化T31发酵液中的活性单体化合物,并根据理化性质和光谱分析（ESI MS、UV、IR、NMR等）鉴定单体化合物结构;采用细胞形态镜检、MTT方法评价单体化合物对人类慢性髓性白血病K562细胞的抗肿瘤活性。结果 从链孢粘帚菌（Gliocladium catenulatum T31）发酵液中分离并鉴定了7个单体化合物,分别为3个甾醇类化合物ergosta-5,7,22-triene-3β-ol（1）、ergosta-6,22-diene-3β-ol（2）、ergosterol peroxide（3）和四个蒽醌类化合物emodin（4）、citreorosein（5）、isorhodoptilometrin（6）和lunatin（7）,化合物1~7对K562细胞显示不同程度的细胞增殖抑制活性,其中,化合物4~7对K562细胞的IC₅₀分别为1.09、1.24、13.6和8.92 μmol·L-1。结论 海洋真菌链孢粘帚菌（Gliocladium catenulatum T31）的主要抗肿瘤活性次级代谢物是甾醇类和蒽醌类化合物。     

簇花清风藤的化学成分研究

目的 研究簇花清风藤Sabia fasciculata枝叶的化学成分。方法 采用硅胶柱色谱、Sephadex LH-20、制备液相等多种色谱技术进行分离纯化,根据理化性质和波谱数据鉴定化合物的结构。结果 从簇花清风藤枝叶95%乙醇提取物中分离鉴定了15个化合物,其中7个五环三萜类化合物：3-氧代-12-烯-28-齐墩果酸甲酯（1）、白桦脂醇（2）、3-氧-Δ^{11, 13(18)}-齐墩果二烯（3）、齐墩果酸（4）、imberic acid （5）、拟人参皂苷RP₁（6）、竹节参苷IVa（7）;3个黄酮类化合物：槲皮素（8）、芦丁（9）、mutabiloside（10）;3个生物碱：5-氧阿朴啡碱（11）、N-p-阿魏酰酪胺（12）、N-反式香豆酰酪胺（13）;2个甾体类化合物：β-谷甾醇（14）、β-胡萝卜苷（15）。结论 所有化合物均为首次从该植物中分离得到,化合物1、5、6、7、10为首次从该属植物中分离得到。     

茶芎地上部位化学成分研究

目的 研究藁本属植物茶芎Ligusticum sinense cv. chaxiong地上部位的化学成分。方法 综合采用硅胶柱色谱、反相柱色谱及制备HPLC色谱等方法进行分离,利用紫外、质谱及核磁共振谱等方法鉴定化合物的结构。结果 从茶芎地上部位的95%乙醇提取物的石油醚和二氯甲烷萃取部位分离得到14个化合物,分别鉴定为5-羟基正丁基苯酞（1）、3-hydroxy-octa-1, 5-dien-7-one（2）、伞形花内酯（3）、pumbinernoid A（4）、crocinervolide（5）、(3R, 6R, 7E)-3-hydroxy-4, 7-megastignadien-9-one（6）、洋川芎内酯G（7）、莨菪亭（8）、(2Z)-3-(3, 4-二羟基苯基)-2-丙烯醛（9）、(3S, 5R, 6S, 7E, 9R)-5, 6-epoxy-3, 9-dihydroxy-7-megastigmene（10）、吐叶醇（11）、二氢猕猴桃内酯（12）、7-羟基正丁基苯酞（13）、洋川芎内酯A（14）。结论 化合物1～13为首次从该植物中分离得到,化合物1、2、4～6和9～13为首次从该属植物中分离得到,化合物1首次作为天然产物分离得到。     

蕨的化学成分研究

 目的 研究蕨（Pteridium aquilinum var.latiusculum）的化学成分。方法 采用多种色谱进行分离,通过波谱方法结合理化性质鉴定其化学结构。结果 从蕨中分离鉴定了16个化合物,分别为：（2R）-蕨素B（1）、（2S,3S）-蕨素C（2）、反式乌毛蕨酸（3）、苏铁蕨酸（4）、槲皮素（5）、异槲皮苷（6）、芦丁（7）、异鼠李素-3-O-（6″-O-E-p-香豆酰基）-β-D-葡萄糖苷（8）、紫云英苷（9）、山柰酚-3-O-芸香糖苷（10）、椴树苷（11）、原儿茶酸（12）、莽草酸（13）、苯甲酸（14）、胡萝卜苷（15）、β-谷甾醇（16）。结论 化合物3、4、8、10、12~14为首次从该植物中分离得到,其中化合物3和4为首次从蕨科植物中发现。     

南海红树林内生真菌ZH-4d代谢产物研究

目的：研究南海红树林内生真菌ZH-4d的代谢产物。方法：采用反复硅胶柱色谱法、Sephadex LH-20凝胶色谱法等进行分离纯化,并通过理化常数测定和光谱分析鉴定其化学结构。结果：从南海红树林内生真菌ZH-4d的培养液中分离得到6个代谢产物。经波谱解析,分别为citrinin（1）,tenellic acid C（2）,tenellic acid A（3）,terretonin（4）,echinulin（5）,（E）-4,6-dimethoxy-3-[4-oxo-5-(prop-1-enyl)-4H-pyran-2-yl]-isobenzofuran-1（3H）-one（6）。初步药理活性显示化合物1对口腔癌细胞KB,KBv200的抗肿瘤活性分别为0.08,0.09 mmol·L^-1。结论：所有化合物均首次从南海红树林内生真菌ZH-4d中分离得到。     

Two novel cytotoxic benzofuran derivatives from Brazilian propolis

Two novel benzofuran derivatives, propolis-benzofurans A (1) and B (2), were isolated from the MeOH extract of Brazilian propolis, together with two known isoprenylated compounds (E)-3-[2, 3-dihydro-2-(1-methylethenyl)-7-prenyl-5-benzofuranyl]-2-propen oic acid and (E)-3-?4-hydroxy-3-[(E)-4-(2, 3-dihydrocinnamoyloxy)-3-methyl-2-butenyl]-5-prenylphenyl?-2 -propenoi c acid. The structures of these compounds were elucidated on the basis of spectral analysis. Both the new compounds exhibited mild cytotoxicity toward highly liver-metastatic murine colon 26-L5 carcinoma and human HT-1080 fibrosarcoma cells.     

Six new diarylheptanoids from the seeds of Alpinia blepharocalyx

Chromatographic separation of part of an EtOH extract of the seeds of Alpinia blepharocalyx resulted in the isolation of six new (1-6) and two known (7, 8) diarylheptanoids together with 12 known compounds. The structures of the new compounds, including their absolute stereochemistry, were elucidated by spectroscopic and chemical methods as (3S,5S)- (1) and (3S,5R)-3-hydroxy-5-methoxy-1-(4-hydroxyphenyl)-7-phenyl-6E-heptene (2), (3S,5S)- (3) and (3S,5R)-3-hydroxy-5-ethoxy-1-(4-hydroxyphenyl)-7-phenyl-6E-heptene (4), (3S)-methoxy-1,7-bis(4-hydroxyphenyl)-6E-hepten-5-one (5), and 1,7-bis(4-hydroxyphenyl)hepta-4E,6E-dien-3-one (6). Among the isolated compounds, 5, (3S,5S)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (8), 4'-hydroxy-5,6-dehydrokawain (14), and/or phloroglucinol (20) showed significant antiproliferative activity against murine colon 26-L5 carcinoma (ED(50): 5, 5.2 microM; 8, 12.8 microM; 14, 20.7 microM; 20, 26.4 microM) and human HT-1080 fibrosarcoma (ED(50): 5, 10.1 microM; 14, 20.1 microM; 20, 20.9 microM) cells.     

Bioassay-guided isolation of constituents of Piper sarmentosum using a mitochondrial transmembrane potential assay

Bioassay-guided fractionation was conducted on a chloroform-soluble extract of the aerial parts of Piper sarmentosum collected in Vietnam, monitored by a mitochondrial transmembrane potential assay using HT-29 human colon cancer cells. This led to the isolation of four new C-benzylated dihydroflavones, sarmentosumins A-D (1-4), as well as 14 known compounds. The structures of the new compounds were elucidated on the basis of spectroscopic data interpretation. Among these compounds, 1-4 as well as five known C-benzylated dihydroflavones (5-9) and a piperamide, pipercallosine (11), were found to induce apoptosis in HT-29 cells by moderately reducing the mitochondrial transmembrane potential (ΔΨm), with ED50 values ranging from 1.6 to 13.6 μM. Furthermore, 7-methoxydichamanetin (8) and pinocembrin (10) exhibited proteasome inhibitory activities in a human 20S proteasome bioassay with IC50 values of 3.45±0.18 and 2.87±0.26 μM, respectively. This is the first time that C-benzylated dihydroflavones have been reported to demonstrate an apoptotic effect associated with disruption of the mitochondrial transmembrane potential.     

Malevamides A-C, new depsipeptides from the marine cyanobacterium Symploca laete-viridis

Three new depsipeptides, malevamides A-C (1-3), were isolated from the cyanobacterium Symploca laete-viridis collected off the south shore of Oahu, Hawaii. Compounds 1-3 were identified by spectral methods, and partial stereochemical assignments were made by chiral HPLC of the hydrolyzed compounds. At a concentration of 2 microg/mL, compounds 1-3 were inactive against P-388, A-549, and HT-29 cancer cells.     

New cytotoxic butanolides from Litsea acutivena.

Six new compounds, including one nor-neolignan, dehydroxymethylailanthoidol (1), and five butanolides, litseakolide D (2), litseakolide E (3), litseakolide F (4), litseakolide G (5), and isolincomolide D (6), were isolated from the leaves of Litsea acutivena. Their structures were elucidated from spectral analyses. The butanolides (2-6) showed significant cytotoxic activity against P-388, A549, and HT-29 cell lines in vitro.     

Lignans from the roots of Saururus chinensis

Four new lignans, saucerneol F (1), saucerneol G (2), saucerneol H (3), and saucerneol I (4), were isolated from the EtOAc extract of the roots of Saururus chinensis, together with one known compound, saucerneol D (5). The structures of compounds 1-4 were elucidated by spectroscopic analysis. These compounds showed cytotoxic activities against HT-29, MCF-7, and HepG-2 cell lines.     

益智仁化学成分的研究

目的:研究益智仁Alpinia oxyphylla的化学成分.方法:采用硅胶和HPLC等色谱手段进行化学成分的分离纯化,根据波谱数据结合理化性质鉴定化合物结构;用SRB法对化合物进行肿瘤细胞毒活性试验.结果:从益智仁的70%丙酮-水提取物中分得8个化合物,鉴定其结构分别为(9E)-humulene-2,3;6,7-diepoxide(1),3(12),7(13),9(E).humulatriene-2,6-diol(2),(-)-oplopanone(3),yakuchinone A(4),yakuchinone B(S),杨芽黄素(6),异香草醛(7),(2E,4E)-6-羟基-2,6-二甲基-2,4-庚二烯醛(8);用肿瘤细胞株A549,HT-29和SGC-7901测定了化合物1,3～5的细胞毒活性.结论:化合物1～3,7,8为首次从该属植物中分离得到;化合物1,3～5 10 mg·L~(-1)对肿瘤细胞株A549,HT-29和SGC-7901未显示出细胞毒活性.     

Structure and cytotoxicity of diterpenoids from Isodon eriocalyx

A new ent-atisanoid, eriocatisin A (1), six new ent-abietanoids, eriocasins B-E (2-4, 7), 3-acetyleriocasin C (5), and 3β-acetoxyeriocasin D (6), and seven new ent-kauranoids, maoesins A-F (8, 10-14) and 3α-acetoxy-maoesin A (9), together with 21 known compounds, were isolated from the aerial parts of Isodon eriocalyx. The structures of 1-14 were determined by spectroscopic data interpretation. All compounds isolated were evaluated for their in vitro growth inhibitory activity against the HT-29, BEL-7402, and SK-OV-3 human cancer cell lines. Compounds 17, 18, and 20 showed inhibitory effects for all three tumor cell lines used, with IC(50) values in the range 2.1-7.3 μM.     

Isolation, structure elucidation, and biological evaluation of 16,23-epoxycucurbitacin constituents from Eleaocarpus chinensis

Eight new 16,23-epoxycucurbitacin derivatives, designated as elaeocarpucins A-H (1-8), and five known cucurbitacins (9-13) were isolated from the chloroform-soluble partitions of separate methanol extracts of the fruits and stem bark of Elaeocarpus chinensis collected in Vietnam. Isolation work was facilitated using a LC/MS dereplication procedure, and bioassay-guided fractionation was monitored using HT-29 human cancer cells. The structures of compounds 1-8 were determined on the basis of spectroscopic data interpretation, with the absolute configurations of isomers 1 and 2 established by the Mosher ester method. Compounds 1-13 were evaluated in vitro against the HT-29 cell line and using a mitochondrial transmembrane potential assay. Elaeocarpucin C (3), produced by partial synthesis from 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one (13), was found to be inactive when evaluated in an in vivo hollow fiber assay using three different cancer cell types (dose range 0.5-10 mg/kg/day, i.p.).     

Metachromins U-W: cytotoxic merosesquiterpenoids from an Australian specimen of the sponge Thorecta reticulata

Three new merosesquiterpenoids, metachromins U, V, and W (1-3), were isolated from a specimen of the marine sponge Thorecta reticulata collected off Hunter Island, Tasmania, Australia. Structures of the new compounds were elucidated through extensive NMR investigations and comparison with literature values. The cytotoxicities of 1-3 were assessed against a panel of human tumor cell lines (SF-268, H460, MCF-7, and HT-29) and a mammalian cell line (CHO-K1). All compounds were found to have 50% growth inhibition activities in the range 2.1-130 μM, with 2 being the most active (GI50 2.1-10 μM).