1株发光杆菌Photorhabdus asymbiotica的次级代谢产物研究

摘要：目的 研究1株发光杆菌Photorhabdus asymbiotica抗革兰阴性菌的活性次级代谢产物。方法 以抗革兰阴性菌活性为导向,采用大孔吸附树脂、MCI柱色谱,以及反相高效液相色谱等多种分离纯化技术,利用HR-ESIMS和NMR等波谱学方法,分离Photorhabdus asymbiotica发酵液中的化合物并鉴定其结构。结果 从菌株Photorhabdus asymbiotica中获得3个次级代谢产物,并鉴定为darobactin(1)、环(L-色氨酸-L-脯氨酸)(2)和环(L-脯氨酸-L-苯丙氨酸)(3)。其中化合物1对大肠埃希菌、肺炎克雷伯菌和鲍曼不动杆菌均具有显著的抗菌活性。结论 化合物1为发光杆菌Photorhabdus asymbiotica中主要的抗革兰阴性菌活性化学成分。     

川牛膝化学成分的研究

目的对川牛膝的化学成分进行研究。方法反复采用大孔树脂、硅胶、反相硅胶、Sephadex LH-20凝胶等色谱法分离化合物,经质谱、核磁等光谱学方法鉴定化合物结构。结果从川牛膝乙醇提取物的大孔树脂洗脱部分中分离得到5个化合物。结论其结构鉴定为：化合物（1）杯苋甾酮;化合物（2）24-羟基杯苋甾酮;化合物（3）森告甾酮;化合物（4）苯基-β-D-吡喃葡萄糖苷;化合物（5）（＋）-莱昂树脂醇-3α-O-β-D-吡喃葡萄糖苷,其中化合物5是首次从该植物中被发现。     

抗病毒抗生素16704A的研究Ⅰ.产生菌的分类、发酵及活性成分的提取、分离与鉴别

在筛选抗病毒抗生素的过程中,从云南土壤分离出的一株链霉菌16704,其发酵液抗HSV-1病毒活性较强,我们对链霉菌16704产生菌的初步分类,发酵,活性成分的提取,分离和鉴别等进行了研究,通过大孔树脂吸附层析,有机溶剂提取,RP-8反相柱层析等方法分离得到16704A纯品,经过对化合物16704A理化性质的测定和对其UV、FAB-Mass、EI-Mass和1H-NMR谱的分析,将其鉴别为已知化合物Bafilomycin A1.     

放线菌HCCB01128的活性代谢产物及菌株鉴定

目的 研究放线菌HCCB01128产生的抗肿瘤活性次级代谢产物.方法 利用系统发育、形态特征和生理生化特性分析的方法对菌株HCCB01128进行初步鉴定.大孔吸附树脂吸附HCCB01128发酵液,反相色谱对菌株次级代谢产物进行分离和纯化.通过质谱、核磁共振氢谱(1H)、碳谱(13C)等分析对化合物1128-1进行结构鉴定.MTT法检测HCCB01128代谢粗提物的肿瘤细胞毒性.结果与结论 菌株HCCB01128的16S rRNA与淀粉酶产色链霉菌Streptomyces diastatochromogenes的16S rRNA具有99.51％的相似性.其发酵初提物具有较强的抗肿瘤活性;经纯化鉴定其中一种活性化合物为Aurodox.本文首次报道从淀粉酶产色链霉菌中分离到Aurodox.     

AB-8大孔吸附树脂分离牛心朴子草的活性成分

目的分离牛心朴子草中的活性成分。方法以牛心朴子草为原料,采用AB-8大孔吸附树脂分离牛心朴子草提取液中的活性成分,利用柱层析、重结晶等方法对活性部分进行分离和纯化。结果对分离得到的化合物采用质谱、红外光谱、紫外光谱和核磁共振谱图进行了表征,证实为7-脱甲氧基娃儿藤碱。结论AB-8大孔吸附树脂可以用于牛心朴子草活性成分的分离。     

链霉菌2754发酵产物的分离提取及结构鉴定

目的 从链霉菌2754中提取分离和纯化小分子VEGF受体抑制剂,并进行结构鉴定.方法 以酪氨酸酶活性测定方法(EuSA法)为活性跟踪方法,利用大孔吸附树脂反相HPLC等方法进行分离纯化.利用光谱分析,进行结构解析.结果 分离纯化到两个七尾霉素类化合物nanaomycin αA和nanaomycin βA并具有相关活性.结论 Nanaomycin αA和nanaomycin βA为己知化合物,首次报道该化合物具VEGFR拮抗活性.     

马鹿茸血疏水性肽的分离及组分3的免疫活性

采用大孔吸附树脂和凝胶色谱等方法,从马鹿茸血蛋白酶解产物中分离纯化获得免疫活性肽.通过体外试验研究其免疫活性.结果表明:大孔吸附树脂可依据氨基酸的疏水性对肽段进行分离,经梯度洗脱后,其中用75%乙醇洗脱所得的组分促脾淋巴细胞增殖活性最高.纯化所得的产物中组分3具有较高的DPPH自由基清除能力,可刺激白介素-1的分泌、促进巨噬细胞的吞噬活性.     

水飞蓟茎叶中具有抗氧化活性的黄酮类化学成分研究

目的:通过已经建立并且行之有效的化学筛选(LC-MSn)和活性筛选集成系统获取水飞蓟茎叶中具有抗氧化活性的黄酮类化合物.方法:95％乙醇提取药材获得总提取物,D101型大孔树脂富集总黄酮类化合物,多种色谱方法(sephadex-LH20,HPLC等)相结合分离得到目标化合物,NMR谱鉴定化合物结构;采用Fe2+半胱氨酸诱导的肝微粒体脂质过氧化模型进行化合物抗氧化活性筛选.结果:从水飞蓟茎叶中首次分离得到5个黄酮类化合物,这5个化合物均具有较强的抗氧化活性,IC50值8.5～11.2.结论:从水飞蓟茎叶中获取的黄酮类化合物具有较强的抗氧化活性,我们将进一步研究抗氧化活性与临床治疗相关疾病的关系.     

野雉尾金粉蕨中一个新的大环黄酮

采用大孔树脂、硅胶、反相硅胶、葡聚糖凝胶及高效液相等色谱法,从野雉尾金粉蕨中分离纯化得到7个化合物。通过核磁共振谱、质谱等波谱学方法分别鉴定为金粉蕨酮A(1)、槲皮素(2)、槲皮素-3-O-α-L-吡喃鼠李糖苷(3)、山柰酚-7-O-β-D-葡萄糖苷(4)、山柰酚-3-O-α-L-吡喃鼠李糖苷(5)、(-)-prunin(6)和1,3,6,7-四羟基酮(7),其中化合物1为结构新颖的大环黄酮类化合物,其余化合物均为首次从该植物中分离得到。采用MTS法测试化合物对5种肿瘤细胞株的细胞毒活性,结果显示化合物7对肺癌A549、肝癌SMMC-7721和结肠癌SW480细胞具有弱的细胞增殖抑制活性。     

海洋放线菌WBF16次级代谢产物的分离与结构鉴定

目的分离和鉴定海洋来源的放线菌WBF16代谢产物中的抗肿瘤活性成分。方法利用大孔树脂、Sephadex LH-20凝胶柱层析、硅胶柱层析、反相柱色谱和HPLC等方法对该放线菌发酵产物进行分离,根据理化性质和波谱学方法进行化学结构的鉴定;利用MTT法来检测化合物的抗肿瘤活性。结果从海洋放线菌代谢产物中分离得到其特征代谢产物色霉素A2(1)和2-甲基-5,6,7-三甲氧基-1,4-萘醌(2)。结论化合物2为新天然产物,化合物1为首次从海洋微生物中分离得到,同时化合物1对人口腔上皮癌KB细胞、人肺癌细胞株A549、人肝癌细胞株SMMC-7721的细胞毒活性较好,IC50值分别为3.81、7.21和12.58μg/L。     

Preparation and antitumor activity of new mitomycin A analogues

A series of 26 mitomycin A analogues including 23 new ones was prepared by a variety of methods. The most useful methods were alkoxide exchange on mitomycin A and treatment of 7-hydroxymitosane with 3-substituted 1-phenyltriazenes. Many of the new analogues were superior to mitomycin C in the P388 leukemia assay and the more stringent subcutaneous B16 melanoma assay both in mice. Four of them gave long-term survivors in the latter assay. Quantitative correlations between log P and antitumor activity were not possible, but some guidelines for future analogue development are proposed.     

A new diimide derivative from the co-culture broth of two mangrove fungi (strain no. E33 and K38)

A new diimide derivative, named ( ? )-byssochlamic acid bisdiimide (1), was isolated from the mixed broth of two mangrove fungi (strain no. K38 and E33) from the South China sea coast. The structure of 1 was determined by comprehensive spectroscopic methods, including 1D and 2D NMR (COSY, HMQC, and HMBC) and semi-synthesis. Primary bioassays showed that 1 had weak cytotoxic activity against Hep-2 and HepG2 cells.     

A new geranyl flavanone from Macaranga triloba

A new geranyl flavanone, 2'-hydroxy-macarangaflavnone A (1), and a known 4',7-dihydroxy-8-methylflavan were isolated from the leaves of Macaranga triloba (Euphorbiceae). The structure of 1 was elucidated based on spectroscopic methods, including 1D and 2D NMR analysis.     

Nephrotoxicity of 4-cycloocten-1-carbaldehyde

Natural and synthetic chemicals are often used in the fragrance industry. A toxicological profile of the synthetic fragrance booster, 4-cycloocten-1-carbaldehyde, was generated using a test program including the following methods: acute oral toxicity, acute dermal toxicity, acute skin and eye irritation, skin sensitization, subchronic toxicity, and mutagenicity. The substance was strongly irritating to the skin but only weakly irritating to the eye. It gave a clear indication of having skin-sensitizing properties. Based on the comprehensive data from a mutagenicity test battery, 4-cycloocten-1-carbaldehyde was assessed to be nonmutagenic. Although its acute toxicological profile shows no toxicity after oral or dermal application, 4-cycloocten-1-carbaldehyde displays a complex toxicological response after repeated dosing over 13 weeks. 4-Cycloocten-1-carbaldehyde or its metabolites show clear nephrotoxic properties focusing on tubular cells of the kidney. In view of these data no no-effect level can be derived from this study with 4-cycloocten-1-carbaldehyde. A broad interaction of the test substance with various tissue types and cell parameters together with severe and irreversible organic defects even at low doses leads to the conclusion that 4-cycloocten-1-carbaldehyde is unsuitable for the intended use in industrial fragrance formulations.     

New sulfoalkylresorcinol from marine-derived fungus, Zygosporium sp. KNC52

A new sulfoalkylresorcinol (1) was isolated from the marine-derived fungus, Zygosporium sp. KNC52. The structure of 1 was elucidated by spectroscopic methods including MS and NMR, and the absolute stereochemistry was determined by the modified Mosher's method. Compound 1 inhibited FtsZ polymerization in vitro and exhibited weak antimicrobial activity against multi-drug-resistant bacteria.     

Flavone c-glycosides from Trollius ledebouri reichb

A new acylated C-glycosylflavone (1) was isolated from Trollius ledebouri Reichb together with two known C-glycosyflavones (2, 3). The structures were elucidated by spectroscopic methods, including HRMS, IR, 1H and 13C NMR and 2D experiments (COSY, HMQC and HMBC). The anti-inflammatory activities of 1-3 were tested on TPA-induced mice ear edema (in vivo).     

Nardonoxide, a New Nardosinane-Type Sesquiterpene Ether from Nardostachys chinensis

A new sesquiterpene ether, nardonoxide ( 1), with the nardosinane skeleton, was isolated from the underground parts of NARDOSTACHYS CHINENSIS Batalin (Valerianaceae), growing in the province Sichuan (China). The structure of 1 was elucidated by spectroscopic methods, including 2D-NMR-spectroscopy.     

头孢呋辛钠的热稳定性及其热分解动力学研究

目的:研究头孢呋辛钠的热稳定性。方法:采用热重分析法和差式扫描量热法测定头孢呋辛钠在氮气和空气中的热分解曲线,借助经典的非等温速率方程Kissinger和Ozawa-Flynn-Wall方法计算该药物的热分解动力学参数。结果:2种方法计算头孢呋辛钠在空气中的热分解动力学参数分别为:表观活化能139.2、139.3kJ.mol-1,指前因子(ln值)18.64、18.66s-1;在氮气中上述参数分别为106.8、108.5kJ.mol-1,14.64、14.85s-1。2种计算方法结果无显著性差异。结论:头孢呋辛钠具有很高的活化能,热稳定性好,在氮气中更稳定。     

New isochaetochromin, an inhibitor of triacylglycerol synthesis in mammalian cells, produced by Penicillium sp. FKI-4942: II. structure elucidation

The structure of a new congener of chaetochromin, an inhibitor of triacylglycerol synthesis in CHO-K1 cells produced by Penicillium sp. FKI-4942, was elucidated by spectroscopic methods, including various NMR experiments. Isochaetochromin A(1) has a bis-naphtho-γ-pyrone moiety.     

Flavonoids from Pyrrosia petiolosa (Christ) Ching

A new kaempferol glycoside, kaempferol-3-O-beta-D-glucopyranoside-7-O-alpha-L-arabinofuranoside (1), was isolated from the EtOH extract of Pyrrosiapetiolosa together with six known flavonoids already reported from the same plant. Structural elucidation was performed by means of physico-chemical methods including MS, and 1D and 2D NMR spectroscopy.