一株红树内生真菌Phomopsis sp. MGF222次级代谢产物及其活性研究

目的 研究一株红树植物木果楝（Xylocarpus granatum Koenig）来源内生真菌Phomopsis sp. MGF222的次级代谢产物及其生物活性。方法 利用硅胶柱层析、Sephadex LH-20凝胶柱层析、半制备HPLC等色谱分离方法，对该菌发酵产物的乙酸乙酯浸膏的次级代谢产物进行分离纯化；综合利用NMR、MS等波谱解析方法以及与文献数据对照，鉴定化合物的结构；并对化合物进行抗菌和α-葡萄糖苷酶抑制活性评价。结果 从内生真菌Phomopsis sp. MGF222中分离鉴定9个化合物(1~9)，结构分别为12-epicitreoisocoumarinol (1)，5-hydroxy-7methoxy-4methylphthalide (2)，5-hydroxy-7-methoxy-4,6-dimethylphthalide (3)，(2-(2"-hydroxypropyl)-5-methyl-7-hydroxychromone (4)，tyrosol (5)，2-hydroxy-benzaldehyde (6)，5-hydroxymethyl-pyrrole-2-carbaldehyde (7)，(2S,2"R,3R,4E,8E,3"E)-2-(2"-hydroxy-3"-octadecenoylamino)-9-methyl-4,8-octadecadiene-l,3-diol (8)，(22E,24S)-5,8-epidioxy-24-methyl-cholesta-6,9(11),22-trien-3-ol (9)；其中化合物9对白色念珠菌Canidia albicans显示抗菌活性；化合物2, 5和8具有α-葡萄糖苷酶抑制活性。结论 发现1个具有抗菌活性和3个具有α-葡萄糖苷酶抑制活性的化合物，具有重要的研究和应用价值。     

荚果蕨植物内生真菌Penicillium sp. SYP-F-7610的抑菌活性次级代谢产物研究

摘要：目的 研究荚果蕨根茎内生真菌Penicillium sp. SYP-F-7610发酵液中抑菌活性次级代谢产物。方法 采用硅胶柱 色谱、ODS柱色谱、反相半制备HPLC等分离菌株发酵液中的次级代谢产物,根据比旋光度和波谱学数据(MS、1H NMR、13C NMR)进行结构鉴定。采用比浊法测试次级代谢产物的抑菌活性。结果 从荚果蕨根茎内生真菌Penicillium sp. SYP-F-7610发 酵液中分离鉴定了7个化合物,分别为青霉酸(1)、3,5,6-三甲基-2,4-二羟基苯甲酸甲酯(2)、苔黑酚(3)、4-羟基苯乙酸甲酯(4)、 6-hydroxy-5-methoxy-3-methyl-3,6-dihydro-2H-pyran-4-carboxylic acid (5)、chermesinone A (6)和(R)-甲羟戊酸内酯(7)。化合物1 对大肠埃希菌(Escherichia coli CMCC44103)、乙型副伤寒沙门菌(Salmonela paratyphi B CMCC50094)、蜡样芽胞杆菌(Bacillus cereus ATCC14579)和肺炎克雷伯菌(Klebsiella pneumoniae CMCC46117)表现出抑制作用,IC50值为3.19~6.79 μg/mL。结论 本文 首次对荚果蕨属植物的内生真菌进行研究,发现荚果蕨根茎内生真菌Penicillium sp. SYP-F-7610的次级代谢产物结构类型丰富、 生物活性多样,值得深入研究。化合物5为首次报道从青霉属真菌次级代谢产物中分离得到。化合物1为首次报道对乙型副伤寒 沙门菌具有抑制活性。     

南极真菌Penicillium sp. S-2-10次级代谢产物的研究

目的 对来源于南极海域海底沉积物（47.09° W,62.05° S,水深1393 m）真菌Penicillium sp. S-2-10的次级代谢产物进行研究。方法 对菌株进行规模发酵,并对所得发酵液的乙酸乙酯萃取浸膏进行系统分离纯化,据化学指征和生物学活性两方面特点,采用Sephadex LH 20凝胶色谱、正相硅胶柱色谱、反相ODS柱色谱、高效液相柱层析等色谱分析方法,通过核磁（1H-NMR和13C-NMR等）及质谱（MS）等波谱分析方法,并与相关文献比较,鉴定化合物结构。 结果 分离得到7个单体化合物,经鉴定化合物1~7分别为Benzoic acid, 2-(2,6-dihydroxybenzoyl)-3-hydroxy-5-(hydroxymethyl)-methyl, methyl ester (1), chrysophanol (2), Volemolide (3), Ergosta-6,8(14),22-trien-3-ol (4), 2-aminophenoxazin-3-one (5), 2-benzothiazolol (6), benzoic acid (7)。结论 化合物3,4为首次从Penicillium属真菌中获得。     

海沟泥样来源真菌Penicillium sp. HDN19010的次级代谢产物研究

目的 研究马里亚纳海沟来源真菌Penicillium sp. HDN19010的次级代谢产物。方法 优化菌株培养条件,运用硅胶柱层析、ODS反相柱层析和半制备高效液相色谱法（HPLC）对其发酵产物进行分离提纯,通过质谱（MS）、核磁共振波谱（NMR）分析及和已报道文献比对,对化合物结构进行解析,并进行抑菌活性评价。结果 从该菌株中分离得到1个新的异戊烯基化的化合物methyl 2-[4-[(E)-4-hydroxy-3-methylbut-2-enoxy]phenyl]acetate(1),1个已知的二酮哌嗪类化合物fusaperazine F(2),2个已知二萜类化合物conidiogenone B～C(3～4)。评价了化合物1～4对10种细菌抑制活性评价,结果表明化合物均无抑菌活性。     

1株红树来源真菌Penicillium sp.次级代谢产物及其生物活性研究

目的 研究1株红树来源真菌Penicillium sp.中的次级代谢产物及生物活性。方法 综合运用硅胶柱层析和半制备型HPLC等方法分离纯化次级代谢产物,利用NMR及MS等现代波谱分析方法鉴定化合物结构,以斑马鱼血管抑制模型对其进行活性评价。结果 在细胞毒活性的指导下,从Penicillium sp.中分离出抗肿瘤活性化合物brefeldin A,同时还分离出5个天然产物,分别是 (+)-semivioxanthin (1)、(-)-striatisporolide A (2)、dibutyl phthalate (3)、bisdethiobis (methylthio)-acetylapoaranotin (4) 和alternarosin A (5)。其中化合物1和3分别在1 μmol/L和10 μmol/L浓度下显示出斑马鱼血管抑制活性,但同时会导致一定的脊柱弯曲。化合物3还具有抑制硅藻附着的潜在防污活性。结论 化合物4和5为首次从真菌Penicillium sp.中分离获得。化合物1和3具有潜在的生物活性。     

真菌Penicillium sp. DT-F27次级代谢产物及其活性研究

摘要：目的 一株海洋来源真菌Penicillium sp. DT-F27次级代谢产物及其抗肿瘤活性的研究。方法 采用硅胶柱色谱、反相高效液相制备色谱等方法,对该真菌发酵产物的乙酸乙酯提取物进行分离纯化;采用波普解析方法对化合物的结构进行鉴定;采用MTT法测定化合物对人前列腺癌PC-3细胞的抗肿瘤作用。结果 从真菌Penicillium sp. DT-F27的发酵物中分离得到15个化合物,分别为麦角甾醇（1）,dehydrocyclopeptine（2）,3-O-methylviridicatin（3）,verrucofortine（4）,cyclopenin（5）,cyclo(dehydroala-L-Leu)（6）,cyclopenol（7）,4-hydroxy-2-methoxy acetanilide（8）,trans-(3RS,4RS)-3,4-dihydro-3,4,8-trihydroxynaphthalen-1(2H)-one（9）,cyclo(D-Pro-D-Val)（10）,brevianamide F（11）,cyclo(L-Pro-L-Val)（12）,anacine（13）,cyclo(L-Orn-L-Tyr-L-Orn-L-Ala)（14）,cyclo(L-Pro-L-Tyr)（15）。结论 从真菌Penicillium sp. DT-F27的次级代谢产物中分离15化合物,其中麦角甾醇（1）和3-O-methylviridicatin（3）具有较强的抗肿瘤活性,抑制率分别为45.6%和34.8%。     

1株红树内生真菌Phomopsis sp. MGGP14112活性次级代谢产物研究

摘 要：目的 研究1株红树植物木果楝（Xylocarpus granatum Koenig）来源内生真菌Phomopsis sp. MGGP14112的次级代谢产物及其生物活性。方法 综合运用硅胶柱层析、Sephadex LH-20凝胶柱层析、半制备高效液相色谱（HPLC）等色谱分离技术对菌株的发酵产物进行分离纯化,通过核磁共振波谱（NMR）、质谱（MS）等多种现代波谱技术以及与文献数据对照,确定化合物的结构,对化合物进行抗氧化活性和抗虫活性测试。结果 从内生真菌Phomopsis sp.中分离鉴定出7个化合物1~7,结构分别为phomoxydiene B (1)、deacetylmycoepoxydiene (2)、mycoepoxydiene (3)、5,6-dihydroxy-2,3,6-trimethylcyclohex-2-enone (4)、4-methoxy-3,6-dimethylpyran-2-one (5)、petasol (6)和lithocarin A (7)。其中化合物3表现出一定的抗氧化活性,其IC50为3.83 mg/mL;化合物1~3和7对棉铃虫幼虫（Helicoverpa armigera Hubner）具有一定的生长抑制活性,其IC50值为200 μg/mL。结论 从红树内生真菌Phomopsis sp. MGGP14112中分离获得7个单体化合物,活性筛选发现1个具有抗氧化活性和4个具有棉铃虫幼虫生长抑制活性的化合物,具有重要的研究和应用价值。     

红树林内生真菌多样性及其次级代谢产物GH-9-1抗肺癌活性的研究

摘 要：目的 分析湛江观海长廊红树林内生真菌多样性,筛选具有抗肺癌活性的内生真菌次级代谢产物,对其中1株内生真菌Penicillium sp. GH-9发酵产物4-甲基-3-甲氧基-2,4-戊二烯酸（GH-9-1）进行抗肺癌活性研究。方法 利用微生物培养和发酵技术对红树林内生真菌进行分离纯化及液体发酵,通过16S rRNA基因序列构建系统发育树分析红树林内生真菌多样性,利用高效液相色谱（HPLC）检测技术对其次级代谢产物进行特征峰追踪分离,根据核磁共振数据鉴定化合物结构,采用CCK-8法、流式细胞术、Western blot技术评价单体化合物的体外抗肺癌活性。结果 从湛江市观海长廊采集6种红树林植物组织标本及红树林根部土壤标本,共分离得到130株内生真菌,从真菌Penicillium sp. GH-9的发酵产物中获得其主要特征性代谢产物4-甲基-3-甲氧基-2,4-戊二烯酸（GH-9-1）。化合物GH-9-1可抑制非小细胞肺癌细胞A549和H460细胞生长增殖,并可诱导A549和H460细胞发生凋亡和细胞周期阻滞。结论 湛江市观海长廊红树林内生真菌具有丰富的多样性,从其中1株内生真菌Penicillium sp. GH-9的次级代谢产物分离得到的GH-9-1具有显著的抗肺癌活性。     

海洋真菌Metarhizium sp. P2100来源的α-吡喃酮类化合物研究

目的 研究1株海洋绿僵菌属真菌新种Metarhizium sp. P2100中具有抗菌活性的次级代谢产物。方法 分别用大米固体培养基、葡萄糖蛋白胨酵母膏（GPY）液体培养基培养真菌,运用硅胶柱层析、凝胶柱层析、高效液相色谱等技术对真菌发酵产物进行分离纯化得到单体化合物,综合运用核磁（NMR）、质谱、旋光（ORD）、圆二色谱（CD）等手段解析其结构,并利用抗细菌模型进行活性筛选。结果 从大米培养基、GPY培养基发酵产物中分离获得了7个吡喃酮类化合物：分别为(S)-6-[(S)-2-hydroxypentanoyl]-4-methoxy-5,6-dihydro-2H-pyran-2-one(1)、LL-P 880γ(2)、(6S,1’S,2’S)-hydroxypestalotin(3)、LL-P880β(4)、(6S)-6-Pentanoyl-4-methoxy-5,6-dihydro-2H-pyran-2-one(5)、PC-2(6)、LL-P 880α(7)。其中化合物1为新化合物,5～7具有中等抗细菌活性,对弧菌、粪肠球菌、耐甲氧西林金黄色葡萄球菌等多种致病菌的最小抑菌浓度（MIC...     

细脚棒束孢(Isaria tenuipes)的化学成分研究

目的对细脚棒束孢Isaria tenuipes次级代谢产物进行研究,为扩大细脚棒束孢的药用资源提供科学依据。方法采用硅胶柱层析,Sephad ex LH-20分离技术进行分离纯化单体化合物,根据理化性质及波谱数据等手段鉴定其结构。结果从细脚棒束孢Isaria tenuipes固体发酵产物的乙酸乙酯提取物中分离得到5个化合物,分别是:4-methoxy-6-entanoyl-2H-pyran-2-one(1),6-(1,2-dihydroxypentyl)-4-methoxy-5,6-dihydro-2H-pyran-2-one(2),6-[(3R)-2,3-dihydr oxybutan-2-yl]-4-methoxy-2H-pyran-2-one(3),(5-hydroxy-2-oxo-2H-pyran-4-yl)methylacetate(4)和6-(1-hydroxypentyl)-4-methoxy-5,6-dihydro-2H-pyran-2-one(5)。结论其中化合物1为新的天然产物。其余化合物均是首次从细脚棒束孢中分离得到。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.