东京枫杨中三萜类化合物的分离鉴定与抗肿瘤活性

目的阐明中国民间用于癌症治疗的中草药东京枫杨的抗癌活性成分.方法以细胞凋亡诱导、坏死性细胞毒活性为抗癌指标,采用硅胶、Sephadex LH-20柱色谱、HPLC和流式细胞术,跟踪分离活性成分,利用理化手段鉴定化学结构;用SRB法及流式细胞术评价化合物的抗癌活性.结果从东京枫杨中分离鉴定了3个具有抗癌活性的三萜类化合物齐墩果酸(1)、2α,3β,23-三羟基齐墩果酸(2)和乌苏酸(3),并对化合物1～3和白桦酯酸(4)的抗癌活性进行了系统评价.化合物1～4在10 mg/L浓度下对K562细胞增殖的的抑制率分别为42.4%、45.2%、33.7%和34.3%.流式细胞术检测表明:化合物3对tsFT210细胞有细胞周期抑制和细胞凋亡诱导作用.结论化合物1～2均为首次从该属植物中分离得到的抗肿瘤活性化合物.     

洋紫荆中生物碱类抗肿瘤活性成分的研究

目的研究洋紫荆中的抗癌活性成分.方法采用色谱法与生物活性追踪相结合分离纯化活性成分.丽丝胺罗丹明B(SRB)法检测化合物对K562细胞增殖的影响,流式细胞仪检测化合物对K562细胞周期的影响.结果分离得到4个具有活性的生物碱类化合物,用现代谱学方法鉴定为N-naphthyl-2-aniline(1)、biocyclomahanimbine(2)、mahanimbine(3)、girinimbine(4).化合物1～3体外具有明显诱导K562细胞调亡作用.结论 4个生物碱类化合物均为该属中首次分离,其中化合物1的体外抗癌活性为首次报道.     

中药大血藤中酚类化学成分及其抗肿瘤活性

目的阐明中药大血藤中抗癌活性成分.方法以细胞周期抑制、坏死性细胞毒活性为抗癌指标,采用硅胶、Sephadex LH-20、大孔树脂HP-20等色谱方法,跟踪分离活性成分,利用理化性质及波谱方法鉴定了化学结构,用SRB法及流式细胞术评价其抗癌活性.结果与结论从大血藤茎中分离得到7个酚酸类化合物:3,5-O-二甲基-没食子酸(1)、原儿茶酸(2)、绿原酸(3)、N-(对-羟基苯乙基)阿魏酸酰胺(4)、对-羟基苯乙醇(5)、(-)-表儿茶素(6)、缩合鞣质B2(7).化合物3对人慢性髓性白血病K562细胞的半数抑制浓度(IC50)为97.2 μg/mL,化合物4在100 μg/mL浓度下对K562细胞的增殖抑制率为46.6%.流式细胞术检测表明,化合物7对小鼠乳腺癌tsFT210细胞和K562细胞均显示G2/M期抑制作用,为一新的细胞周期抑制剂.除化合物2外,其余6个化合物均为首次从该属植物中分离得到.     

长叶水麻的三个酚酸类化学成分及其抗肿瘤活性

目的阐明民间用于癌症治疗的长叶水麻Debregeasia longifolia(Burm.f.)Wedd.的化学成分及其抗肿瘤活性.方法用小鼠乳腺癌tsFT210细胞的流式细胞术筛选模型,确定抗肿瘤活性部位;利用大孔树脂HP-20、Sephadex LH-20、硅胶等柱色谱和制备HPLC色谱等技术,分离精制活性部位的化学成分;根据理化性质和波谱数据鉴定化合物的化学结构,用流式细胞术评价其抗肿瘤活性.结果与结论从长叶水麻活性部位分离鉴定了没食子酸(1)、3,5-二甲氧基没食子酸-4-O-β-D-吡喃葡萄糖苷(2)和(-)-表儿茶素(3)等3个酚酸类化合物,其中,化合物1具有细胞周期G2/M期抑制活性.化合物1和2系首次从长叶水麻中分离得到,1为该植物抗肿瘤活性成分的首例报道.     

海洋来源黄直丝链霉菌产物中新细胞周期抑制剂的研究

目的 研究海洋来源黄直丝链霉菌Z4-007产物中的抗肿瘤活性成分。方法 采用流式细胞术筛选模型与分离技术紧密结合的活性跟踪分离模式，以细胞周期抑制活性为抗肿瘤指标，分离纯化活性成分；根据理化常数及波谱数据鉴定化学结构；用流式细胞术测试化合物活性。结果 从黄直丝链霉菌Z4-007发酵物中分离得到4个活性化合物，其中1个鉴定为1-（2，4-二羟基-3，5-二甲基苯基）-（2E，4E）-己二烯-1-酮（1），其余3个初步推测为环肽类化合物。用小鼠乳腺癌tsFT210细胞经用流式细胞术测试分析结果表明：化合物Ⅰ在高浓度时将细胞周期抑制在G0／G1期，而在低浓度时则抑制在G2／M期并显示出一定的细胞凋亡诱导活性。结论 化合物Ⅰ为首次从链霉菌属的微生物产物中分离得到，是一个新的细胞周期抑制剂。     

方榄抗癌活性成分的研究--酚酸类细胞周期抑制剂

摘要：目的阐明中国民间用于癌症治疗的中草药方榄的抗癌活性成分。方法 以细胞周期抑制活性为抗癌指标，采用硅胶、Sephadex LH-20、ODS等柱色谱和流式细胞术，跟踪分离活性成分，利用谱学手段鉴定化学结构。结果与结论 从方榄茎皮中分离鉴定了5个具有细胞周期抑制活性的酚酸类化合物：没食子酸(1)、没食子酸乙酯(2)、没食子酸甲酯(3)、鞣花酸(4)和1，2，3，4，6-五没食子酰基-β-D葡萄糖(5)。这些化合物抑制tsFT210细胞周期的MIC值为73．5μmol／L(1)、15．2μmoL，L(2)、16．3μmol／L(3)、20．7μmol／L(4)、6．6μmol／L(5)，其中1和3为新细胞周期抑制剂。化合物1～5均为首次从方榄中得到，化合物2、3、5系首次从该属植物中分离得到。     

南酸枣的芳香族化合物及其体外抗肿瘤活性

目的阐明南酸枣的抗肿瘤活性成分.方法通过活性跟踪分离确定活性组分,利用各种色谱技术分离活性组分中的化学成分.根据理化性质和光谱数据鉴定结构,利用SRB法和流式细胞术评价单体化合物的抗肿瘤活性.结果从南酸枣树皮中分离鉴定了5个化合物,分别为乔松素(1)、柚皮素(2)、白杨素(3)、邻苯二甲酸二丁酯(4)和反式阿魏酸十四酯(5).SRB法测试结果:化合物1～5在10μmol·L-1浓度下对HCT-15细胞增殖的抑制率分别为21.5%(1)、37.3%(2)、33.1%(3)、20.1%(4)和17.0%(5),而在相同浓度下对HeLa细胞的抑制率分别为30.0%(1)、22.1%(2)、22.4%(3)、30.4%(4)和26.4%(5).流式细胞术测试结果:化合物1和2对tsFT210细胞有较弱的G2/M期抑制作用,化合物4在高浓度时表现坏死性细胞毒活性,而在低浓度时则具有G0/G1期抑制活性.结论化合物1和3～5为首次从该属植物中分得,化合物1～5系首次报道的该植物中具有抗癌活性的5个成分.     

黑紫藜芦化学成分研究

目的 研究黑紫藜芦(Veratrum japonicum Loes.f.)的化学成分.方法 利用酸碱处理及硅胶柱色谱进行系统分离,通过理化性质和波谱数据鉴定结构;利用黄鸣龙反应还原主要成分介藜芦碱.结果 分离并鉴定了其中5个化合物,分别是正二十八烷醇(1)、β-谷甾醇(2)、表红介藜芦碱(3)、胡萝卜苷(4)、介藜芦碱(5);还原介藜芦碱得到抗肿瘤活性物质环巴胺.结论 化合物1～4均为首次从该植物中分离得到;首次利用黄呜龙反应还原介藜芦碱,并得到一个副产物3-表环巴胺.     

海洋来源的放线菌3295代谢产物的结构鉴定及抗肿瘤活性(Ⅰ)

目的 对海洋来源的放线菌3295代谢产物中的抗肿瘤活性成分进行分离和鉴定。方法 利用细胞周期抑制为抗肿瘤活性指标，采用Sephadex LH—20．硅胶和HPLC等柱色谱技术对3295活性菌株发酵物进行活性追踪分离，根据理化性质和光谱方法进行化学结构鉴定，用流式细胞术评价化合物的抗肿瘤活性。结果与结论 从其代谢产物中分离得到1个具有抗肿瘤活性的化合物I，结构鉴定为邻苯二甲酸二丁酯(dibutylphthalate)；化合物Ⅰ对小鼠乳腺癌温敏型tsFT210细胞具有G0／G1期细胞周期抑制作用。     

洋紫荆中菲醌化合物bauhinione对K562细胞的增殖抑制作用

目的探讨从洋紫荆中分离得到的新的菲醌化合物bauhinione对体外培养的人类慢性骨髓性白血病K562细胞的增殖抑制作用。方法应用罗丹明B法检测bauhinione对癌细胞K562和tsFT210的抑制作用;采用形态学观察以及流式细胞术(FCM)检测该化合物对K562细胞的细胞周期抑制和诱导凋亡作用;通过倍量稀释法考察该化合物的最小抑制质量浓度及其质量浓度为12.5mg.L-1时的时效关系。结果Bauhinione对两种癌细胞的IC50值分别为(24.9±2.1)mg.L-1和(111.36±3.5)mg.L-1,说明K562细胞对bauhinione的作用敏感;Bauhinione对K562细胞的最小抑制质量浓度为6.25mg.L-1;对K562细胞的增殖抑制作用是通过G2-M期抑制和诱导凋亡实现的,并与时间呈依赖关系。结论Bauhinione在体外有抑制K562细胞增殖的作用,为洋紫荆的抗癌活性成分之一。     

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.