皱瘤海鞘化学成分研究△

目的 对皱瘤海鞘的化学成分进行研究。方法 用色谱法以及光谱技术分离鉴定其化学成分。结果 从皱瘤海鞘中分离得到12个化合物,分别鉴定为：邻苯二甲酸二异丁酯(1)、邻苯二甲酸二丁酯(2)、邻苯二甲酸双(2-甲基)庚酯(3)、5-羟基-3,4-二甲基-5-戊基呋喃-2(5H)-酮(4)、5-羟基-3,4-二甲基-5-丙基呋喃-2(5H)-酮(5)、9-十八碳烯酸-2’,3’-二羟基丙酯(6)、2’-脱氧尿嘧啶核苷(7)、2’-脱氧胸腺嘧啶核苷(8)、乙基-α-D-吡喃葡萄糖苷(9)、尿嘧啶核糖核苷(10)、腺嘌呤核糖核苷(11)、2’-脱氧腺嘌呤核苷(12)。结论：其中10个化合物均为首次从该种海鞘中分离得到。     

两株海鞘来源放线菌 Streptomyces coelicoflavus和 Nocardiopsis dassonvillei的次级代谢产物及其生物活性研究

目的 从采自中国黄海的威海海域的柄海鞘来源放线菌Streptomyces coelicoflavus(HQA809) 和史氏菊海鞘来源放线菌Nocardiopsis dassonvillei(HQA404) 中分离、鉴定具有生物活性的次级代谢产物。方法 运用硅胶柱层析、Sephadex LH-20凝胶柱层析和半制备HPLC等方法分离化合物,运用核磁、质谱等现代波谱分析方法对化合物进行结构鉴定,并对化合物进行抗菌、卤虫致死、α-糖苷酶抑制活性和细胞毒活性评价。结果 从 Streptomyces coelicoflavus(HQA809) 中分离鉴定了2个吡喃酮类化合物 (1,2),从 Nocardiopsis dassonvillei(HQA404) 中分离鉴定了1个吩嗪类化合物 (3) 和1个苯酚类化合物 (4);化合物3对鳗弧菌 (Vibrio anguillarum) 和副溶血弧菌 (Vibrio parahaemolyticus) 显示出较强的抑菌活性,其MIC值分别为50 μmol/L和25 μmol/L。结论 海鞘来源放线菌可以作为发现新颖的生物活性物质的潜在来源。     

一株枝网刺柳珊瑚共附生真菌Peniophora sp.次级代谢产物研究

目的对一株中国南海枝网刺柳珊瑚Echinogorgiasp.共附生真菌Peniophorasp.的次级代谢产物及生物活性进行研究。方法利用硅胶柱层析、凝胶柱层析、重结晶和半制备HPLC等方法,对发酵产物乙酸乙酯相进行分离纯化;采用NMR、MS等波谱分析方法并结合文献数据,鉴定化合物的结构;通过卤虫致死活性模型和斑马鱼胚胎毒性模型评价化合物的生物活性。结果从真菌Peniophorasp.中分离得到7个甾体化合物,分别鉴定为:4-hydroxy-17R-methylincisterol(1),麦角甾醇(2),(3β,5α,6β,22E)-6-甲氧基麦角甾-7,22-二烯-3,5-二醇(3),酒酵母甾醇(4),麦角甾-4,6,8,22-四烯-3-酮(5),过氧化麦角甾醇(6)和9(11)-脱氢过氧化麦角甾醇(7)。结论化合物1显示出较强的卤虫致死活性,在25μg.mL-1浓度下,对卤虫Artemia salina的致死率为88.4%;化合物4显示较强的鱼毒活性,对斑马鱼Danio rerio胚胎脊索畸形毒性的EC50值为7.83μg.mL-1(72h)。     

黏萼蝇子草蜕皮甾酮类成分的分离与鉴定

目的对黏萼蝇子草根的化学成分进行研究。方法采用反复硅胶柱色谱、Sephadex LH-20柱色谱和反相半微量制备型高效液相色谱分离纯化,根据ESI-MS、1H-NMR和13C-NMR等谱学数据进行结构鉴定。结果从黏萼蝇子草根的乙醇提取物分离得到5个蜕皮甾酮类化合物,分别鉴定为20-羟基蜕皮激素(20-hydroxyecdysone,1)、1-epi-integristerone A(2)、abutasterone(3)、旌节花甾酮A(stachysterone A,4)和15-羟基旌节花甾酮A(15-hydroxystachysterone A,5);另外得到胡萝卜苷(daucosterol,6)和β-谷甾醇(β-sitosterol,7)2个甾醇类化合物。结论化合物2-5为蝇子草属植物中首次分离的化合物。     

中国南海侧扁软柳珊瑚Subergorgia suberosa次级代谢产物

目的研究中国南海侧扁软柳珊瑚Subergorgia suberosa的次级代谢产物。方法利用硅胶柱层析、Sephadex LH-20凝胶柱层析、HPLC等方法对化合物进行分离纯化;利用NMR,MS等波谱方法,并与文献对照,鉴定化合物的结构;利用抗菌活性模型和卤虫致死活性模型评价化合物的生物活性。结果从侧扁软柳珊瑚中分离鉴定了6个单体化合物,分别为:倍半萜化合物subergorgic acid(1),2-β-hydroxysubergorgic acid(2)和2-β-acetoxysubergorgic acid(3);甾体化合物3β-hydroxy-5α-pregnan-20-one(4),5α-pregnane-3,20-di-one(5)和胆甾醇(6)。结论化合物1～3对白色葡萄球菌Staphylococcus albus均显示出较强的抑制活性,化合物4对蜡状芽孢杆菌Bacillus cereus显示出较强的抑制活性,而化合物4和5显示出较强的卤虫致死活性。     

芫花花蕾中甾醇类化合物的分离与鉴定

目的对瑞香科瑞香属植物芫花(Daphne genkwa Sieb.et Zucc.)花蕾中的甾醇类化学成分进行分离与结构鉴定。方法运用硅胶﹑Sephadex LH-20柱色谱﹑重结晶等分离手段进行甾醇类化合物的分离纯化,根据理化性质及波谱数据鉴定其化学结构。结果从芫花花蕾的体积分数95%乙醇提取物中分离得到6个化合物,分别鉴定为:豆甾-5-烯-3β,7α-二醇(stigmasta-5-ene-3β,7α-diol,1)、豆甾-5-烯-3β,7β-二醇(stigmasta-5-ene-3β,7β-diol,2)、豆甾-4-烯-3β,6β-二醇(stigmasta-4-ene-3β,6β-diol,3)、7-ketositosterol(3β-hydroxysitost-5-ene-7-one,4)、过氧化麦角固醇(ergosterol peroxide,5)和β谷甾醇-3β-吡喃葡萄糖苷-6'-O-棕榈酸酯(β-sitosteryl-3β-glucopyranoside-6'-O-palmitate,6)。结论化合物2⁶为首次从瑞香属植物中分离得到,化合物1为首次从芫花植物中分离得到。     

海洋真菌zp6次级代谢产物及其抗真菌活性研究

目的对海洋真菌zp6发酵液的乙酸乙酯萃取部分及其抑菌活性进行研究。方法采用硅胶柱色谱及高效液相色谱进行分离纯化,根据理化性质及各种光谱技术进行结构鉴定,采用滤纸片法对分离到的化合物进行抑菌活性研究。结果从该菌中分离纯化得到8个化合物:(22E)-3β,5α,9α-三羟基-麦角甾-7,22-二烯-6-酮(1)、5α,8α-环二氧-24-甲基麦角甾-6,22-二烯-3β-醇(2)、赤藓糖醇(3)、腺嘌呤核苷(4)、(24R)-麦角甾-7,22-二烯-3β,5α,6β-三醇(5)、阿拉伯醇(6)、(7)、4-乙酰氧基苯甲酸(8)。结论化合物1和5具有抗真菌活性。     

密花石豆兰的化学成分研究

目的对密花石豆兰(Bulbophyllum odoratissimum Lindl.)60%(ψ)乙醇提取物中的化学成分进行分离鉴定.方法利用硅胶、ODS及大孔树脂HP-20等多种柱色谱方法对密花石豆兰的60%(ψ)乙醇提取物进行分离,以反相HPLC进行纯化.根据化合物的理化常数、波谱学特征鉴定化合物的结构.结果从密花石豆兰的60%(ψ)乙醇提取物中分离得到了1个木脂素类化合物和5个酚酸类化合物,利用理化常数和波谱学分析鉴定为( )-lyoniresinol-3a-O-β-D-glucopyranoside(I)、苔色酸乙酯(Ⅱ)、3-甲氧基-4-羟基-桂皮醛(Ⅲ)、4-羟基-3,5-二甲氧基-苯甲醛(Ⅳ)、对羟基苯丙酸(V)和对羟基苯丙酸甲酯(Ⅵ).结论这6个化合物均为首次从该属植物中分离得到.     

广东石豆兰的化学成分研究

目的:对广东石豆兰(Bulbophyllum kwangtungense Schltr)60%乙醇提取物乙酸乙酯萃取层中的化学成分进行分离鉴定.方法:采用硅胶、ODS等多种柱色谱方法,对广东石豆兰的60%乙醇提取物的乙酸乙酯萃取层进行分离,以反相HPLC进行纯化.根据化合物的理化常数、波谱学特征并参考文献,鉴定了化合物的结构.结果:从广东石豆兰的60%乙醇提取物的乙酸乙酯层中,分离得到了3个菲类化合物和2个9,10二氢菲类化合物,利用理化常数和波谱学分析鉴定为Bulbophyllanthrin(Ⅰ)、2,3,4-三甲氧基-5-羟基菲(Ⅱ)、2,3,4,5-四甲氧基菲(Ⅲ)、Coelonin(Ⅳ)和2,4,7-三甲氧基-9,10-二氢菲(Ⅴ).结论:化合化Ⅴ为首次从该属植物中分离得到,其余4个化合物均为首次从该种植物中分离得到.     

三宝木枝条抗菌活性成分的分离与鉴定

目的研究三宝木(Trigonostemon chinensis Merr.)枝条的化学成分。方法采用多种柱色谱技术进行分离纯化,通过理化性质和波谱数据分析鉴定化合物的结构,采用滤纸片琼脂扩散法测定化合物抗菌活性。结果从三宝木枝条乙醇提取物的乙酸乙酯萃取物中分离得到了12个已知化合物,经波谱分析鉴定为松脂醇(1)、(+)-de-4″-O-methylmagnolin(2)、丁香脂素(3)、nitidanin(4)、臭矢菜素A(5)、6-deoxyjacareubin(6)、巴西红厚壳素(7)、豆甾-4,22-二烯-3-酮(8)、3β-羟基豆甾-5-烯-7-酮(9)、豆甾-4-烯-3-酮(10)、正十八酸(11)、β-谷甾醇(12)。结论 12个化合物均为首次从该植物中分离得到,其中,化合物2、4、5、8、9、10是首次从该属植物中分离得到。初步抗菌活性结果表明化合物7对金黄色葡萄球菌、烟草青枯菌具有抑制活性。     

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.     

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.