穿心莲内酯3,19-缩醛（酮）衍生物对小鼠脾淋巴细胞增殖活性的影响*

目的:评价穿心莲内酯及其衍生物对小鼠脾淋巴细胞增殖活性的影响,用于指导以穿心莲内酯为先导化合物的新型免疫调节剂的合成。方法:采用MTT法,在1.56~12.50μmol.L-1定量考察穿心莲内酯及其3,19-缩醛(酮)衍生物对小鼠脾淋巴细胞增殖反应的影响。结果:穿心莲内酯对丝裂原诱导的淋巴细胞增殖活性有显著的抑制作用。通过半合成改造得到的3,19-缩醛(酮)衍生物可使抑制活性显著提高,但是部分衍生物在1.56~6.25μmol.L-1内表现出促进T或/和B淋巴细胞增殖的作用。结论:穿心莲内酯3,19-缩醛(酮)衍生物对穿心莲内酯作为开发免疫调节剂的先导化合物有重要价值和潜力。     

穿心莲内酯衍生物抗肿瘤、解热抗炎构效关系研究进展

目的对近年来穿心莲内酯衍生物抗肿瘤、解热抗炎的构效关系研究进展综述,为穿心莲内酯的进一步研究提供思路。方法对相应文献进行归纳、总结和综述。结果穿心莲内酯及其衍生物发挥抗肿瘤活性的必需基团是完整的α-亚烷基-γ-丁内酯,Δ12,13双键,Δ8,17双键或成环及C14羟基等活性基团;而α-亚烷基-γ-丁内酯环打开与否和抗炎无关,穿心莲内酯及其衍生物的双键位置决定其抗炎作用,具有环内双键的化合物抗炎作用强于具有环外双键的化合物。结论穿心莲内酯衍生物具有良好的开发前景,应加强其衍生物与构效关系的研究。     

固态穿心莲内酯的降解

穿心莲Andrographis paniculata(Burm.f.)Wall.ex Nees.主要活性成分是穿心莲内酯(1)及其衍生物脱氧穿心莲内酯(2)、新穿心莲内酯(3)和14脱氧-11,12-二脱氢穿心莲内酯(4)等三萜内酯。该植物地上部分干粉在干燥环境中贮存一年以上,其总内酯含量减少26％。作者研究了穿心莲内酯在高温条件下的稳定性和可能的主要降解途径。     

连续应用穿心莲内酯致急性肾功能衰竭一例

穿心莲内酯及其衍生物广泛应用于临床，主要用于抗病毒治疗。关于肾损害的不良反应报道较多，该例患者因有既往过敏史而再次应用穿心莲内酯的不同衍生物而致严重的肾功能衰竭。本病例为研究穿心莲内酯的毒性作用提供参考，同时对于临床杜绝使用商品名有典型的警示作用。     

异穿心莲内酯3,19-双酯类衍生物的合成与表征

目的 设计并合成异穿心莲内酯衍生物.方法 以DCC为缩合剂,DMAP为催化剂,合成异穿心莲内酯3,19-双酯衍生物.结果 合成并表征了9个异穿心莲内酯3,19-双酯衍生物及2个异穿心莲内酯19-单酯衍牛物.异穿心莲内酯与羧酸及缩合剂DCC的摩尔比为1.0;2.5;2.5,于室温下反应4～6 h.结论 所合成化合物结构均经1HNMR、MS确证.     

穿心莲内酯脂质体体外细胞毒性实验

穿心莲内酯（andrographolide）是穿心莲的主要有效成分之一，具有抗菌解热、止咳平喘等作用，临床用于治疗上呼吸道炎症和细菌性痢疾，疗效较好，且副作用小。然而，穿心莲内酯难溶于水，口服生物利用度较低，为提高其在水中的溶解度，穿心莲内酯及其衍生物注射液处方中加入了大量的增溶剂，但后者会增加制剂的毒性。     

穿心莲内酯糖苷衍生物的合成

目的:合成穿心莲内酯糖苷衍生物.方法:对穿心莲内酯的羟基进行糖苷化,合成了穿心莲内酯-葡萄糖苷,穿心莲内酯-半乳糖苷,穿心莲内酯-甘露糖苷.结果与结论:目标化合物经IR、HNMR、MS得到结构确证,可能具有更强的抗艾滋病的潜力.     

穿心莲内酯及其衍生物制剂临床作用特点与不良反应评析

目的了解穿心莲内酯及其衍生物制剂临床作用特点的差异性,为临床合理用药提供参考。方法依据4种制剂的说明书并查阅相关文献资料,从其成分、药理作用及适应症、用法用量、使用溶媒、注意事项、配伍禁忌、不良反应等方面进行比较。结果以穿心莲内酯为基本结构的4种制剂临床作用特点及不良反应存在一定差异。结论临床应加深对穿心莲内酯衍生物不同注射剂作用特点及不良反应的认识,合理选择使用不同制剂,保障用药安全。     

穿心莲内酯类化合物的分析研究——Ⅰ.穿心莲内酯(Andrographolide)衍生物的离子对高速液相色谱法分析

本文报道了穿心莲内酪的各种水溶性衍生物,如亚硫酸氢钠加成穿心莲内酯,亚硫酸钠加成穿心莲内酯,穿心莲内酯磺酸钠与三乙酰化穿心莲内酯磺酸钠,及其制剂的离子对高速液相色谱法。以0.08%十六烷基三甲基溴化铵(Cetrimide)为对离子,以异丙醇-正戊醇-水(65:27:7)为流动相,pH3～4,硅胶柱,紫外λ220nm为检测器,可使各种衍生物获得完全分离与分别定量。本法准确度与专属性好,最低检出量为1×10^-5g,选择苦味酸为内标,由数据站系统自动存贮并计算分析结果。     

穿心莲内酯衍生物AL-1合成工艺中杂质的分离与鉴定

目的：分离和分析穿心莲内酯衍生物AL-1合成中的杂质,探讨其来源及成因,并以此指导合成工艺改进。方法：采用色谱法分离和分析AL-1合成中的杂质;MS和1H NMR进行结构确证。结果：杂质分别为二羟基缩丙酮保护的穿心莲内酯脱水物和脱水穿心莲内酯。结论：穿心莲内酯14-位羟基在碱性以及较高温度条件下易脱水生成脱水穿心莲内酯。     

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.     

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.     

Emerging drugs for epilepsy

Epilepsy affects ≤ 1% of the world's population. Antiepileptic drugs (AEDs) are the mainstay of treatment, although more than a third of patients are not rendered seizure free with existing medications. Uncontrolled epilepsy is associated with increased mortality and physical injuries, and a range of psychosocial morbidities, posing a substantial economic burden on individuals and society. Limitations of the present AEDs include suboptimal efficacy and their association with a host of adverse reactions. Continued efforts are being made in drug development to overcome these shortcomings employing a range of strategies, including modification of the structure of existing drugs, targeting novel molecular substrates and non-mechanism-based drug screening of compounds in traditional and newer animal models. This article reviews the need for new treatments and discusses some of the emerging compounds that have entered clinical development. The ultimate goal is to develop novel agents that can prevent the occurrence of seizures and the progression of epilepsy in at risk individuals.     

盐酸达泊西汀中甲磺酸甲酯、甲磺酸乙酯及甲磺酸异丙酯的顶空毛细管GC-ECD法测定

建立了衍生化顶空毛细管气相色谱-电子捕获检测器(ECD)法测定盐酸达泊西汀中的甲磺酸甲酯(MMS)、甲磺酸乙酯(EMS)和甲磺酸异丙酯(IMS).应用碘化钠衍生技术,使用PW-5毛细管柱,载气为氮气,ECD检测,程序升温.MMS、EMS和IMS分别在0.03～0.30、0.05～0.50和0.05～0.50 μg/ml浓度范围内线性关系良好,平均回收率分别为63.5％、100.3％和96.2％,最低检测限分别为0.30、0.50和0.50 ng/ml.     

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.