8-羟基染料木素及其甲基化衍生物的合成与抗缺氧活性研究

目的 制备8-羟基染料木素及其甲基化衍生物，并考察其抗氧化和抗缺氧活性，初步阐明其构效关系。方法 以鹰嘴豆芽素A为原料，经甲基化、溴代、甲氧基化和去甲基化等反应，得到8-羟基染料木素(化合物Ⅰ)及3个甲基化衍生物(化合物Ⅱ～Ⅳ);用DPPH自由基清除实验测定4个目标化合物的自由基清除活性；CCK-8法考察其对缺氧PC12细胞的保护作用，于光镜下观察经目标化合物处理后的细胞形态，比色法测定细胞上清液中乳酸脱氢酶(LDH)的活性。结果 目标化合物Ⅰ～Ⅳ的结构通过对比文献或经NMR、MS等波谱手段确认，HPLC检测纯度均>98%。化合物Ⅰ、Ⅱ对DPPH自由基有较好的清除作用。除化合物Ⅳ外，化合物Ⅰ～Ⅲ均可显著提高缺氧PC12细胞的存活率，降低LDH的活性，维持细胞形态，减轻缺氧对PC12细胞的损伤，其活性顺序为：Ⅰ>Ⅱ>Ⅲ>Ⅳ。结论 8-羟基染料木素及其甲基化衍生物的DPPH自由基清除活性及对缺氧PC12细胞的保护作用随着分子结构中酚羟基数目的增加而增强，提示这些化合物的自由基清除作用可能是其发挥抗缺氧活性的主要机制，其中，8-羟基染料木素的活性最佳。     

菝葜多酚类成分抗氧化活性的研究

目的 对菝葜中天然多酚类化合物的抗氧化活性进行研究,探讨多酚类化合物在菝葜药效发挥中的作用机制. 方法 分别采用TEAC法和DPPH法对菝葜醋酸乙酯部位中分离得到的9个天然多酚类化合物单体（SCE 1～9）的抗氧化活性进行测定,并初步分析它们发挥抗氧化作用的构效关系. 结果 化合物SCE 1～9具有很强的抗氧化活性,均能有效地清除ABTS•+和DPPH自由基,其中化合物SCE 1的活性最强,其清除ABTS•+自由基的TEAC值为（3.11±0.04）mmol•L^-1,在浓度50 μmol•L^-1时对DPPH自由基的清除能力为（95.95±0.76）%. 结论 菝葜中天然多酚类化合物可能是菝葜根茎醋酸乙酯提取物发挥治疗作用的物质基础.     

1-阿魏酰基-4-取代苄基哌嗪盐酸盐的合成及其清除羟自由基活性

以阿魏酸、哌嗪和取代氯苄为原料,合成了11个结构新颖的1-阿魏酰基-4-取代苄基哌嗪盐酸盐;用邻二氮菲-Fe2+氧化法测定目标化合物的体外清除羟自由基活性。结果显示11个目标化合物均具有不同程度的清除羟自由基活性,并初步讨论其构效关系。     

滇重楼活性物质的分离鉴定与体外药理作用的研究

研究滇重楼中甾体皂苷类化合物的体外抗肿瘤作用.采用硅胶柱层析、凝胶色谱、制备高效液相色谱(P-HPLC)及高效液相色谱(HPLC)等分离手段,对滇重楼各溶剂萃取部分进行了分离纯化,得到了7个甾体化合物.本实验在前期实验证明滇重楼乙酸乙酯和正丁醇提取物具有一定的抗肿瘤作用的基础上,以LA795小鼠肺腺癌细胞为研究对象,进一步考察了分离鉴定的单体化合物的抗肿瘤作用.结果表明,单体化合物1～7均表现出对LA795细胞生长的抑制作用;化合物1、2对LA795细胞具有明确的抑制作用,化合物3～7对LA795细胞具有较强的细胞毒活性.讨论了细胞毒活性与化合物结构之间的构效关系,即皂苷元C-3位连接糖链时,糖的数目及种类、连接方式及组成类型对其生物活性都起着至关重要的作用.     

枸杞糖缀合物及糖链的化学结构与免疫活性

为研究枸杞多糖的化学结构 ,免疫活性并探讨其构效关系 ,应用色谱法 ,凝胶过滤法和十二烷基磺酸钠 聚丙烯酰胺凝胶电泳 (SDS PAGE)技术从枸杞粗多糖 (LBP)中分离纯化了 5个组分 (LBP1 LBP5) ,并进一步从LBP1,LBP3,LBP4中纯化得到组分均一的糖缀合物LbGp1,LbGp3和LbGp4及其糖链LbGp1 OL ,LbGp3 OL和LbGp4 OL ,用甲基化 ,部分酸水解和核磁共振 (NMR)技术基本阐明了其化学性质 ,糖组成 ,氨基酸组成及主要结构特征 ,并用小鼠脾细胞增殖反应研究免疫活性表明 ,6个样品均具有直接增强小鼠脾细胞增殖反应的作用 .结果提示 ,枸杞子中具有免疫活性的有效成分是一类结构复杂的糖缀合物 ,其糖链部分可能是其发挥免疫活性的主要活性结构 .     

紫杉醇类似物的合成及抗肿瘤活性

Sinenxan A(SIA)为生物合成法得到的新紫杉烷化合物。为寻找有抗肿瘤活性的新型taxol类似物,对SIA进行结构修饰.设计合成了10个化合物,在母核中引入四氢呋喃环,在14β-位或10β-位连接taxol/taxotere侧链,部分化合物显示一定的抗肿瘤活性。并讨论了这类化合物的构效关系。     

藻酸双酯钠及其分级产物免疫调节作用比较研究

目的探讨海洋药物藻酸双酯钠(PSS)的免疫调节作用及其构效关系。方法采用体外免疫细胞培养法检测PSS及其分级产物的免疫调节作用,根据分级产物结构差异,探讨PSS分级产物的免疫活性构效关系。结果PSS能够促进脾脏淋巴细胞的增殖,提高巨噬细胞吞噬功能,同时能抑制刀豆蛋白A(ConA)及脂多糖(LPS)促进的免疫细胞的增殖作用。结论PSS具有显著的免疫调节作用,不同的糖链长度对免疫细胞作用不同。     

1株链霉菌产胞外多糖ZS-11的结构表征及抗氧化活性研究

目的 对来源于南海深海海泥链霉菌Streptomyces pratensis OUCMDZ-3159所产胞外多糖的结构和抗氧活性进行研究。方法 利用醇沉法和柱色谱法对菌株所产胞外多糖进行分离纯化,利用多种仪器分析方法,包括PMP柱前衍生高效液相色谱法、红外光谱法和气相质谱联用法等分析了多糖的化学组成和结构,通过测定DPPH自由基清除活性、超氧阴离子自由基清除活性、羟基自由基清除活性和还原能力,对多糖的抗氧化活性进行评价。 结果 从链霉菌Streptomyces pratensis OUCMDZ-3159发酵液中得到了1种分子量为25.0 kDa的多糖组分ZS-11,它是由甘露糖和半乳糖以14.5:1的比例构成;糖链中包含(1→)-Manp,(1→2)-Manp,(1→3)-Manp,(1→6)-Manp,(1→2,3)-Galf和(1→2,6)-Manp连接方式;多糖ZS-11具有良好的抗氧化活性,在测定的4种活性指标中,清除DPPH自由基的能力最强。结论 首次从深海海泥放线菌Streptomyces pratensis OUCMDZ-3159中分离得到抗氧化活性显著的胞外多糖ZS-11,它是1种结构新颖的半乳甘露聚糖。     

松花粉抗氧化活性与主要成分的关联分析

目的:研究松花粉的抗氧化活性及其主要有效部位.方法:采用紫外分光光度法测定不同来源松花粉清除DPPH和羟基自由基的能力,及其总黄酮、总甾醇和总多糖的含量,并进行多元相关分析.结果:松花粉提取液对DPPH与羟基自由基均有清除作用,且都呈明显的量效关系;松花粉与破壁松花粉清除DPPH的平均IC50分别为14.86 g·L-1、12.95 g·L-1,清除羟基自由基的平均IC50分别为20.31 g·L-1、3.45 g·L-1;松花粉总黄酮、总甾醇的含量与清除DPPH自由基、羟基自由基的IC50呈负相关,并以总黄酮的相关性最为突出,而总多糖的含量则与其关联性不显著.结论:松花粉具有一定的抗氧化活性,其有效部位为黄酮和甾醇;松花粉破壁能有效提高其清除自由基的能力及总黄酮、总甾醇的含量.     

一种快速筛选非甾体抗炎剂清除羟自由基的方法

近来研究表明,很多抗炎剂有清除羟自由基的作用。抗炎剂布洛芬能防止铁介导的氧化物和类脂过氧化物的形成;5-氨基水杨酸能抑制fenton过程中羟自由基的形成。苯甲酸酯、西咪替丁、β-受体阻滞剂和减少钙离子代谢的药物也具有清除羟自由基作用。抗炎活性和羟自由基清除作用之间无明显相关性,但抗炎剂清除羟自由基活性随着酯链长度的增加而减少。本文介绍了一种用于筛选非甾体抗炎剂与     

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.