白首乌化学成分的研究

自白首乌主要品种耳叶牛皮消(Cynanchum auriculatum Royle ex Wight)根中首次分得三个已知甾体酯型甙元:告达亭(caudatin),开德甙元(kidjolanin),萝藦甙元(Metaplexigenin)和一种新的二苯酮衍生物(Ⅳ),经光谱分析推定其结构为2,6,2′,5′-四羟基,3-乙酰基,6′-甲基二苯酮,命名白首乌二苯酮。     

黄芩甙衍生物的合成及抗人免疫缺陷病毒活性研究

为了评价黄芩甙中糖的存在和糖的种类对抗HIV活性的影响,由天然黄芩甙出发制备了黄芩甙元和5,6-O-二苄基黄芩甙元,并合成了5-羟基-6-O-苄基黄酮-7-β-D-葡萄糖甙(12),5-羟基-6-O-苄基黄酮-7-β-D-半乳糖甙(13),5-羟基-6-O-苄基黄酮-7-α-D-甘露糖甙(14),5-羟基-6-O-苄基黄酮-7-α-D-阿拉伯糖甙(15)。以上化合物及部分中间体的生物活性试验表明:黄芩甙及黄芩甙元均抑制免疫缺陷病毒逆转录酶(HIV-1RT)及在细胞培养中抑制HIV-1;黄芩甙及黄芩甙元的6-位羟基被遮蔽则丧失抑制HIV-1RT活性,说明6-羟基为抑制HIV-RT活性所必需;黄芩甙元抑制HIV-1活性及细胞毒性均强于黄芩甙,两种化合物治疗指数相近。     

白射干黄酮类成分的研究

首次从鸢尾科鸢尾属植物白花射干(Iris dichotoma Pall.)根茎中分离出七个黄酮类化合物。根据理化常数及光谱数据,证明成分Ⅰ为一新异黄酮5,3′-dihvdroxy-4′,5′-dimetheoxy-6,7-methylene-dioxyisoflavone,命名为自射干素(dichotomitin),成分Ⅱ为次野鸢尾黄素(irisflorentin),成分Ⅲ为汉黄芩素(wogonin),成分Ⅳ为鼠李秦素(rhamnazin),成分Ⅴ为野鸢尾甙元(irigenin),成分Ⅵ为鸢尾甙元(tectorigenin),,成分Ⅶ为鸢尾甙(tectoridin)。     

紫红獐牙菜中紫药苦甙的结构

继续报道从紫红獐牙菜Sivertia punicea Hemsl,全草中分得的另八个化合物(Ⅰ～Ⅷ)的结构,经光谱解析,I的结构推定为6′-O-β-D-吡喃葡萄糖基獐牙菜甙(6′-O-β-D-glucopyranosylsweroside,Ⅰ),为一新的裂环环烯醚萜甙类化合物,命名为紫药苦甙(swertiapunimarin),Ⅱ～Ⅷ的结构分别鉴定为獐牙菜甙(sweroside,Ⅱ)、獐牙菜苦甙(swertiamarin,Ⅲ)、齐墩果酸(oleanolic acid,Ⅳ)、胡萝卜甙(daucosterol.Ⅴ)、β-谷甾醇(B-sitosterol,Ⅵ)、2,3-二羟基-1,4-苯二甲酸(2,3-dihydroxy-1,4-benzodicarboxylic acid,Ⅶ)及methylswertianin.以上均首次从该植物中得到。     

金翼黄芪甙A的化学结构和绵毛黄芪甙ⅩⅤ及7,2′-二羟基-3′,4′二甲氧基异黄烷-7-O-β-D-葡萄糖甙二维核磁共振谱的研究

从金翼黄芪中分离出金翼黄芪甙A(Ⅰ),绵毛黄芪甙XV (Ⅱ),7,2′-二羟基-3′,4′-二甲氧基异黄烷-7-O-β-D-葡萄糖甙(Ⅲ),大豆皂甙Ⅰ,胡萝卜甙及β-谷甾醇。Ⅰ为新化合物,确定其结构为3-O-[α[-L-鼠李吡喃糖基(1→2)-D-木吡喃糖基]-环黄芪醇。并应用二维核磁共振相关谱对Ⅱ和Ⅲ的~1H和~(13)C化学位移信号进行了全面归属。     

甘肃黄芩中的新黄酮——甘黄芩甙元的结构

本文报道从唇形科植物甘肃黄芩(Scutellaria rehderiana Diels)的根中分得五种黄酮类成分。其中一个新黄酮类化合物(Ⅰ)命名为甘黄芩甙元(ganhuangenin)其结构测定为5,7,3′,6′-四羟基-8,2′-二甲氧基黄酮,其余四种分别鉴定为黄芩甙、汉黄芩素、黄芩黄素和千层纸甲素。     

葛根中异黄酮含量的薄层光密度法测定

本文报道了葛根中异黄酮成分含量的薄层光密度测定法。用甲苯—甲醇—10%甲酸(7:3:0.02)和乙酸乙酯—甲醇—50%甲酸(8:2:0.2)为展开剂,在硅胶G薄层上分离了大豆甙元、大豆甙、葛根素和大豆甙元-4′,7-二葡萄糖甙,并用CS-910双波长薄层扫描仪进行了定量测定。变异系数为1.5～1.6%,采用本法测定了生药和片剂样品的含量。     

金翼黄芪甙A的化学结构和绵毛黄芪甙ⅩⅤ及7,2′-二羟基-3′,4′二甲氧基异黄烷-7-O-β-D-葡萄糖甙二维核磁共振谱的研究

从金翼黄芪中分离出金翼黄芪甙A(Ⅰ),绵毛黄芪甙XV (Ⅱ),7,2′-二羟基-3′,4′-二甲氧基异黄烷-7-O-β-D-葡萄糖甙(Ⅲ),大豆皂甙Ⅰ,胡萝卜甙及β-谷甾醇。Ⅰ为新化合物,确定其结构为3-O-[α[-L-鼠李吡喃糖基(1→2)-D-木吡喃糖基]-环黄芪醇。并应用二维核磁共振相关谱对Ⅱ和Ⅲ的¹H和¹³C化学位移信号进行了全面归属。     

苦绳的甾体成分

从苦绳(Dregea sinensis Hemsl.)中分离到两个新化合物∶苦绳甙元乙(dresigeninB,1)和苦绳甙I(dresiosideI,2)。经光谱和化学反应确定其结构为∶20-O-(2-甲基丁酰基) 托曼托甙元[20-O-(2-methylbutyryl)-tomentogenin]和二氢肉珊瑚甙元3-O-β-D-吡喃黄夹糖基(1-4)-β-D-吡喃夹竹桃糖基(1-4)-β-D-吡喃磁麻糖甙[dihydrosarcostin 3-O-β-D-thevetopyranosyl(1-4)-β-D-oleandropyranosyl(1-4)-β-D-cymaropyranoside]。     

苯妥英氧化后的GLC分析:一种常规测定血药浓度的经济方法

作者将苯妥英(Phenytoin)的氧化产物二苯酮,用GLC 法在以3%OV-17填充的层析柱上进行测定。内标为重结晶的螺(芴-9,4-咪唑烷)2′5′-二酮(1)或5-(4′-甲氧苯基)-5-苯基-2,4-咪唑烷二酮(2),两者经氧化后,分别得9-芴酮(3)、和4-甲氧二苯酮(4)、苯妥英(5)。取0.1或0.2ml 苯妥英血浆样品,置50ml 园底烧     

Na+/K+-ATPase α subunits as new targets in anticancer therapy

Background: The sodium pump (Na⁺/K⁺-ATPase) could be a target for the development of anticancer drugs as it serves as a signal transducer, it is a player in cell adhesion and its aberrant expression and activity are implicated in the development and progression of different cancers. Cardiotonic steroids (CS) are the natural ligands and inhibitors of the sodium pump and this supports the possibility of their development as anticancer agents targeting overexpressed Na⁺/K⁺-ATPase α subunits. Objectives: To highlight and further develop the concept of using Na⁺/K⁺-ATPase α1 and α3 subunits as targets in anticancer therapy and to address the question of the actual usefulness of further developing CS as anticancer agents. Conclusions: Targeting overexpressed Na⁺/K⁺-ATPase α subunits using novel CS might open a new era in anticancer therapy and bring the concept of personalized medicine from aspiration to reality. Clinical data are now needed to further support this proposal. Furthermore, future medicinal chemistry should optimize new anticancer CS to target Na⁺/K⁺-ATPase α subunits with the aim of rendering them more potent and less toxic.     

PROTON AND POTASSIUM TRANSPORT BY H+/K+-ATPases

1. H⁺/K⁺-ATPases are members of the P-type ATPase multigene family. The prototypical H⁺/K⁺-ATPase is the protein that acidifies gastric luminal contents. The physiological and pharmacological significance of this pump has led to a detailed investigation of its biochemistry and molecular and cell biology. 2. Recently, a number of closely related H⁺/K⁺-ATPase isoforms have been discovered. These isoforms are present in organs other than the stomach, including the colon and kidney, where they contribute to acid—base and potassium homeostasis. The structure, expression and physiological roles of the gastric H⁺/K⁺-ATPase and other isoforms are reviewed.     

Kinetics of the Binding of Salicylazosulfapyridine to Human Serum Albumin

Abstract In order to elucidate the possibility of the dissociation rate of drugs from plasma proteins presenting a rate limiting step in the elimination of drugs by secretion (renal or biliary) and metabolism, the kinetics of salicylazosulfa-pyridine (SASP) binding to human serum albumin (HSA) has been investigated by stopped-flow photometry. Equilibrium dialysis showed that HSA has three classes of binding sites for SASP with 0.93, 2.3 and 8.4 sites, respectively, and association constants of 2.1 · 10⁶, 1.4 · 10⁵ and 3.0 · 10³ M^-1, respectively. The association rate constants for the first and second classes are 4.4 · 10⁶ and 1.5 · 10⁷ M^-1 sec.^-1, and the dissociation rate constants are 2.1 and 109 sec.^-1. At SASP concentrations resulting from the usual therapeutic doses about 83 % will bind to the first class binding sites. The dissociation “half time” for this class being 0.34 sec., leads to the conclusion that dissociation rates of this order of magnitude are unlikely to reduce the rate of metabolism or biliary secretion whereas it may reduce renal tubular secretion. Whether this is the case depends on the intrinsic rate constant of secretion.     

SIMULATION OF ACTION POTENTIAL DAMPING PRODUCED BY ANTICONVULSANT DRUGS

Anticonvulsant drugs reduce the ability of central neurones to sustain high-frequency repetitive firing of action potentials. In recent years, it has been demonstrated that this effect is primarily due to a Na⁺conductance reduction. We have simulated the electrical behaviour of a neurone, including Ca²⁺and various K⁺conductances. Although a reduction of Na⁺conductance produces a progressive reduction until a complete suppression of the action potential bust, a smaller reduction of this conductance is necessary to produce the same effect when the delayed-rectifier K⁺conductance and the Ca²⁺conductance are concomitantly reduced . The results indicate that the drugs action on conductances other than Na⁺is important for determining their anticonvulsant effect on neurones at therapeutic concentrations.     

Intracellular and extracellular ammonium (NH4 +) uptake and its toxic effects on the aquatic biomonitor Fontinalis antipyretica

The objective of this work is to validate the use of the aquatic moss Fontinalis antipyretica as biomonitor of NH₄ ⁺ aquatic pollution. In order to achieve this objective we needed to understand the pattern of uptake of NH₄ ⁺ by the moss and evaluate the impact of high concentrations on its physiological performance. The cellular location of NH₄ ⁺ in the moss is crucial for understanding its monitoring capacity. We were able to show that a sequential elution technique, based on the use of NiCl₂ as an efficient displacing agent, allowed the quantification of the cellular location of NH₄ ⁺. This was done along a concentration gradient and time of exposure. The extracellular and intracellular NH₄ ⁺ concentrations that caused significant physiological impact in membrane permeability of F. antipyretica were the same that caused significant decreasing in the photosynthetic capacity of the same moss. The former NH₄ ⁺ concentration thresholds were shown to decrease with increasing exposure time. These results are important since under natural conditions lower concentration of NH₄ ⁺ are present in waters but for very long periods of time. The importance of applying this knowledge in biomonitoring studies to fulfil the requirements of the Water Framework Directive is discussed.     

Efficient gallium‐68 radiolabeling reaction of DOTA derivatives using a resonant‐type microwave reactor

Gallium‐68 (⁶⁸Ga, t_1/2 = 68 min) can be easily obtained from a ⁶⁸Ge/⁶⁸Ga generator, and several such systems are commercially available. The use of positron emission tomography (PET) imaging using ⁶⁸Ga‐labeled radiopharmaceuticals is expected to increase in both preclinical and clinical settings. However, the chelation between a ⁶⁸Ga cation and the bifunctional macrocyclic chelates that are used for labeling bioactive substances, such as 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA), requires a relatively long reaction time and high temperature to achieve a high radiochemical yield. Previously, we reported on a novel resonant‐type microwave reactor that can be used for radiosynthesis and the usefulness of this reactor in the PET radiosynthesis of ¹⁸F. In the present study, the usefulness of this resonant‐type microwave reactor was evaluated for the radiolabeling of model macrocyclic chelates with ⁶⁸Ga. As a result, microwave heating of resonant‐type microwave reactor notably improved the rate of the ⁶⁸Ga labeling chelate reaction in a short time period of 2 minutes, compared with the use of a conventional heating method. Additionally, it was found that the use of this reactor made it possible to decrease the amount of precursors required in the reaction and to improve the molar activity of the labeled compounds.     

Inhibition of acetylcholine-stimulated secretion in the isolated whole stomach of the rat

The rat isolated whole stomach preparation has been used to investigate acetylcholine-stimulated pepsin secretion. Acetylcholine stimulated pepsin output in a dose dependent manner over the range 3 times 10^?4 to 3 times 10^?3 M. Metiamide (10^?3 M) had no significant effect on the pepsin response to acetylcholine suggesting that histamine H₂-receptors are not involved in this response. Atropine (2 times 10^?8, 2 times 10^?7 and 2 times 10^?6 M) produced a dose-related inhibition of the pepsin output to 7 times 10^?4 M acetylcholine, indicating that this response is mediated by muscarinic receptors. Pirenzepine also produced a dose-related inhibition of acetylcholine (7 times 10^?4 M) stimulated pepsin output at 2 times 10^?6, 2 times 10^?5 and 2 times 10^?4 M. Increasing the concentration of acetylcholine to 3 times 10^?3 M completely reversed the effect of atropine (2 times 10^?6 M) but pirenzepine (2 times 10^?4 M) still produced a significant inhibition of acetylcholine-stimulated pepsin secretion. In each series of experiments acid and pepsin secretion responded in a similar manner to the effects of inhibitors, providing no evidence for a separation of these responses.     

POTASSIUM CHANNELS IN VASCULAR SMOOTH MUSCLE

1. Regulation of smooth muscle membrane potential through changes in K⁺ channel activity and subsequent alterations in the activity of voltage-dependent calcium channels is a major mechanism of vasodilation and vasoconstriction, both in normal and pathophysiological conditions. The contribution of a given K⁺ channel type to this mechanism of vascular regulation depends on the vascular bed and species examined. 2. Multiple K⁺ channels are present in most vascular smooth muscle cells and these different K⁺ channels play unique roles in regulating vascular tone. Voltage-dependent K⁺ (Kv) channels are activated by depolarization, may contribute to steady state resting membrane potential and are inhibited by certain vasoconstrictors. Calcium-activated K⁺ (K_Ca) channels oppose the depolarization associated with intrinsic vascular tone and are activated by some endogenous vasodilators. Small-conductance, apamin-sensitive K_Ca channels may be activated by endothelium-derived hyperpolarizing factor. ATP-sensitive K⁺ (K_ATP) channels are activated by pharmacological and endogenous vasodilators. Inward rectifier K⁺ (K_ir) channels are activated by slight changes in extracellular K⁺ and may contribute to resting membrane potential. 3. Membrane potential and diameter are determined, in part, by the integrated activity of several K⁺ channels, which are regulated by multiple dilator and constrictor signals in vascular smooth muscle.