植物内生真菌HCCB00189代谢产物研究

目的：研究植物内生真菌HCCB00189的代谢产物。方法：采用溶剂萃取、硅胶柱层析及制备HPLC等方法，对活性菌株的发酵物进行分离，并根据理化性质和光谱分析对化学结构进行鉴定。结果：从其代谢产物中分离到5个化合物，鉴定为4-甲基苯甲酸羧甲基酯（1）；4-甲氧甲酰基苯甲酸（2）；4-羟甲基苯甲酸（3）；4’，7-二羟基异黄酮（4）和4’，5，7-三羟基异黄酮（5）。抗肿瘤活性测试表明化合物4，5对肿瘤细胞有较明显的抑制作用。结论：从植物内生真菌HCCB00189代谢产物中分离到抗肿瘤活性成分。     

假奓包叶的抗菌活性成分

目的研究假奓包叶的抗菌活性成分。方法在抗菌药理活性跟踪下,应用多种色谱技术进行化合物分离,运用波谱分析法和化学手段鉴定其结构。结果从具有明显抗菌活性的部位分离得到了8个化合物,分别鉴定为洋芹素(1)、木樨草素(2)、穗花杉双黄酮(3)、丹皮酚(4)、脱镁叶绿素a(5)、132S-羟基脱镁叶绿素a(6)、β-谷甾醇(7)、豆甾醇(8)。结论化合物4-6为首次从假奓包叶属植物中得到。药理实验表明,化合物1-6有一定的抑制大肠杆菌的活性;化合物4-6为首次从假奓包叶属植物中得到。药理实验表明,化合物1-6有一定的抑制大肠杆菌的活性;其中化合物3-6还具有抑制金黄色葡萄球菌的活性,化合物4活性最显著。     

苦石莲化学成分研究

目的：系统研究苦石莲的化学成分，为进-步开发苦石莲和制定苦石莲药材定量分析标准提供科学根据。方法：利用硅胶、凝胶和制备薄层等常规色谱分离方法进行化合物分离，采用波谱技术和化学方法鉴定化合物的结构，并对苦石莲各萃取物、水溶部位和caesalmin C（化合物2）进行了流感甲型病毒活性的抑制作用试验。结果：从苦石莲乙醇提取物中分离得到9个化合物，分别鉴定为norcaesalnin E（化合物1）、caesalmin C（化合物2）、5-羟甲基-2-呋喃醛（化合物3）、胡萝卜苷（化合物4）、蔗糖（化合物5）、β-谷甾醇（化合物6）、硬脂酸（化合物7）、咖啡酸十八醇酯（化合物8）、2，5-二羟基苯甲酸乙酯（化合物9），活性试验结果表明，乙酸乙酯萃取物和化合物2对流感甲型病毒活性的抑制作用最强。结论：除化合物2外，其他8个化合物均为首次从该植物中分离得到；化合物2可以作为有效成分定量分析苦石莲质量。     

红树植物卤蕨化学成分的分离与鉴定

目的 对红树植物卤蕨（Acrostichum aureurm）的化学成分进行研究。方法 用多种色谱技术对化合物进行分离纯化。并根据化合物的理化性质及波谱数据鉴定化合物的结构。经MTT法进行体外抗肿瘤活性测试。结果 从卤蕨乙醇提取物中分离得到6个化合物，分别鉴定为ponasteroneA（1）、pterosterone（2）、山奈酚（3）、槲皮素（4）、4-（3。4-二羟基苯基）-2-丁酮（5）、胡萝卜苷（6）。结论 6个化合物均为首次从该植物中分离得到。初步的药理试验表明6个化合物对小鼠B16细胞均无生长抑制活性。     

乌金草化学成分研究

目的提取和鉴定乌金草中活性化学成分。方法采用硅胶柱色谱和Sephadex LH 20凝胶柱色谱对乌金草中化合物进行分离得到单体，通过理化常数和波谱分析方法鉴定其结构。结果从乌金草中分离并鉴定4个化合物：马兜铃内酰胺Ⅰ、9-甲氧基马兜铃内酰胺Ⅳ、β-谷甾醇、1-二十八烷醇。结论4个化合物均为首次从该植物中分离得到。     

萝芙木中化学成分的研究

为研究夹竹桃科植物萝芙木的化学成分及药理活性,通过硅胶、凝胶LH-20、反相开口柱等色谱方法进行分离纯化。根据化合物的理化性质和波谱数据鉴定化学结构,从氯仿层提取物中分离得到3个吲哚类生物碱和1个吖啶酮类生物碱,分别鉴定为萝芙碱B(1)、山德维辛碱(2)、萝尼生(3)和7-羟基-吖啶酮(4)。化合物1为新化合物,属于吲哚类生物碱。化合物4是吖啶酮类生物碱,为首次从萝芙木属植物中分离得到的化合物类型。本文对化合物4这一新类型的生物碱做了生物活性研究,以发掘萝芙木除降压以外其他的药理活性。     

中药祖师麻的三种基源植物的化学及药理活性

对中药祖师麻3种基源植物进行了系统的化学和药理学比较研究。采用现代技术分离黄瑞香、陕甘瑞香和结香中的化学成分，鉴定了63个（次）单体化合物的结构。以小鼠为模型，对上述3种植物的不同提取部位及部分单体化合物进行了抗炎和镇痛活性筛选。研究表明，3种基源植物在化学成分和药理活性方面存在较大的差异。     

光叶合欢中生物碱类和邻苯二甲酸二酯类抗癌活性成分

目的阐明光叶合欢的抗癌活性成分.方法以细胞凋亡诱导和细胞周期抑制活性为抗癌指标,采用柱色谱、薄层色谱等分离技术并结合流式细胞术,跟踪分离活性成分,利用谱学方法鉴定化学结构.结果从光叶合欢中分离鉴定了布木柴胺K(1)、( )-9-去甲布木柴胺K(2)、邻苯二甲酸二丁酯(3)、邻苯二甲酸二(2-乙基-己基)酯(4)和β-谷甾醇(5).化合物1～4显著诱导K562细胞凋亡,在低浓度时还将细胞周期抑制在G0/G1期.结论化合物2为新化合物,化合物1～5为首次从该植物中分离得到,其中1～4为该植物活性成分的首例报道.     

城南细辛化学成分研究(Ⅰ)

目的研究城南细辛的活性化学成分.方法利用柱层析方法分离化合物,理化性质以及光谱方法(UV、IR、NMR、MS)鉴定化合物.结果从城南细辛中离分得3个化合物,鉴定为1-细辛脂素(Ⅰ),1-芝麻脂素(Ⅱ)和β-谷甾醇(Ⅲ).结论化合物Ⅰ、Ⅱ、Ⅲ均为首次从该植物中分离得到.     

红树植物卤蕨内生真菌Penicillium sp.0935030中的抗菌活性成分研究

为研究红树林植物卤蕨（Acrostichum aureurm）内生真菌Penicillium sp．0935030发酵物中的抗菌活性成分，采用活性追踪的方法，用多种色谱技术对化合物进行分离纯化．通过理化性质和光谱数据鉴定出7个化合物，分别为：环（脯氨酸-苏氨酸）（1）．环（脯氨酸-酪氨酸）（2），1-呋喃基-1，2-乙二醇（3），（3p．4B，22B）-12-烯-3，22，23-三羟基-齐墩果烷（4），甘露醇（5），尿苷（6）和甘草素（7）。以上化合物均为首次从该真菌中分离得到。用滤纸片琼脂扩散法测定上述化合物的抗菌活性，其中化合物1、2和7具有明显抗金葡菌和耐甲氧西林金葡菌活性。     

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.