二环杂环化合物热重排反应的意外副产物7-甲硫基-4-甲基-2H-色烯-2-酮及其抗HBV活性

目的 利用7-二甲基硫代氨甲酰氧基-4-甲基-2H-色烯-2-酮(3)高温下的热重排反应制备7-二甲基氨甲酰基硫基-4-甲基-2H-色烯-2-酮(5).方法 热重排反应.结果 除了得到期望的7-二甲基氨甲酰基硫基-4-甲基-2H-色烯-2-酮(5)产物外,还分离得到意外的副产物7-甲硫基-4-甲基-2H-色烯-2-酮(7),其结构经波谱确证.对该副产物进行抗-HBV生物活性测定,显示出显著的抗HBV活性.结论 7-二甲基硫代氨甲酰氧基-4-甲基-2H-色烯-2-酮(3)在高温下产生7-甲硫基-4-甲基-2H-色烯-2-酮(7)副产物,未见文献报道,并对其产生的机制进行探讨.首次报道了7-甲硫基-4-甲基-2H-色烯-2-酮(7)的抗HBV活性.     

气相色谱法同时测定大蒜素原料药中三硫二丙烯、二硫二丙烯及有关物质的含量

目的 建立一种同时检测大蒜素原料药指标成分及有关物质的气相色谱方法。方法 用HP-5弹性石英毛细管柱及程序升温技术,以苯乙酮为内标,正己烷为溶剂,FID检测器检测,内标法计算三硫二丙烯、二硫二丙烯含量,面积归一化法计算有关物质的量。结果 三硫二丙烯回收率98.71%,RSD=0.86%;二硫二丙烯回收率97.28%,RSD=1.33%。结论 该方法简单、快速、准确,可用于大蒜素原料药含量测定及有关物质的限度控制。     

大蒜中一个新的二硫化物结构的研究

从大蒜（Allium Sativum L.)环己烷提取物中分得了一个新的二硫化物，E－丙烯醛基烯丙二基二硫化物（1）；两个新的阿霍烯类化合物：E－4，5，9－三硫－1，7，11－三烯－9，9－二氧化物（2），Z－2，3，7－三硫－4，9－二烯－7－氧化物（3），应用现代波谱技术确定了它们的化学结构。     

色普龙

[通用名称 ]　cyproteroneacetate ,醋酸环丙孕酮[化学名称 ]　 6 氯 1α ,2α 亚甲基 4 ,6 孕甾二烯 17α 羟基 3,2 0 二酮 17 醋酸酯　　 [理化性质 ]　本品为白色或微黄色片剂。[药理作用 ]　本品是一种抗雄激素制剂 ,兼具孕激素和抗促性腺激素样作用 ,因此可抑制垂体促性腺激素的分泌 ,降低血中睾酮的浓度。实验证明 ,本品具有双重抗雄激素作用 ,外周作用可在靶细胞水平竞争结合雄激素受体 ,抑制雄激素活性 ;中枢作用可通过对下丘脑 垂体轴负反馈 ,抑制促性腺激素(LH)分泌 ,使睾酮水平降低 ,降低性欲及性功能 ,减低精子生成量…     

关于大蒜和大蒜素质量标准的商榷

国家药品标准W S-10001-(HD-0050)-2002中规定大蒜素为三硫二丙烯,本文对大蒜中含硫有机化合物的转化途径及药理作用进行综述,说明大蒜素与大蒜虽然名称相似,但并非大蒜中的天然成分,而是蒜氨酸与蒜酶接触降解出的含硫有机化合物,后改由合成得到,因此在中国药典2010年版一部收载的大蒜药材标准中测定三硫二丙烯含量应进行修订。目前国内合成的大蒜素为丙烯基多硫化物的混合物,建议对其质量标准进行修订并取消大蒜素该名称,改为直接采用化学名称三硫二丙烯进行命名。大蒜中很多含硫有机化合物的命名混乱,造成文献中的研究成果无法准确表述,建议对大蒜中含硫有机化合物的命名进行规范。     

硝基呋喃腙类结构和抗血吸虫作用关系的初步探讨

本文根据硝基呋喃腙对小白鼠血吸虫病具有預防作用的发現,合成了数十种同型和同烯系物,进行了化学結构与抗血吸虫作用关系的初步探討。发現5-硝基呋喃-2-甲醛縮硫氨脲、5-硝基呋喃-2-丙烯醛縮氨脲和縮硫氨脲以及β-(5-硝基呋喃-2-)-丙烯酰-(4-甲基)-(口派)嗶嗪、(4-苄基)-(口派)嗶嗪、(4-二乙氨基甲酰)-(口派)嗶嗪、甲胺和乙烯亚胺等8种化合物对小白鼠体內血吸虫童虫具有抑制生长的作用,后两种还兼具对成虫的治疗作用。     

11-酮基-△~9-炔诺酮的合成

在甾体分子的9-位、11-位引入二个双键往往可以增强或改变其生理活性,例如18-甲基三烯炔诺酮与三烯炔诺酮均有比母体18-甲基炔诺酮与炔诺酮更强的抗生育活性。将11-位双键改为11-位酮基,即在11-位引入氧原子,则有抗着床与降胆固醇作用,11-酮基-△~9-炔诺酮(9)100ν对大鼠有抗着床作用,法国Roussel-Uclaf公司进行了全合成,并作简单报道。我们采用炔诺酮中间体,19-羟基-△~4-雄甾烯-3,17-二酮(1)为原料,用半合成路线仅8步反应合成了化合物(9)。     

二烯丙三硫治疗食管癌的疗效观察

二烯丙三硫(Ait)是存在于多种蔬菜中的一种化合物。近年来国内外许多学者发现其具有抗癌作用,但目前都处于基础研究阶段,临床应用的研究未见报道。为此我们将其应用于中晚期食管癌患者得到较好疗效。1 材料与方法①二烯丙三硫:连云港东风制药厂生产,批号911004。②胃镜:olympus GIFXQ20。③病历选择:经病理或胃镜确诊的中晚期不愿或不宜手术食管癌31例、贲门癌6例,其中男34例,女3例,年龄50—75岁,分别在门诊或住院观察。④方法:按常规胃镜检查,通过胃镜活检孔插入注射针,将 Ait 以每点注射0.     

正交实验法确定大蒜提取液中蒜油的β-环糊精包合工艺

大蒜提取液是从百合科葱属植物大蒜Allium sativumL．的地下鳞茎中提取的脂溶性和水溶性成分的混合物,具有抗菌、消炎、活化细胞、清除羟自由基和超氧阴离子自由基的作用,临床用于抗感染、心血管疾病、抗衰老等。本品主要成分大蒜素（三硫二丙烯）,性质不稳定,挥发性强,     

3,5-甾二烯化合物的合成及抗早孕活性

以18-甲基-17β-羟基-17α-乙炔基-雌甾-4-烯-3-酮(18-甲基炔诺酮),17β-羟基-17α-乙缺基-雌甾-4-烯-3-酮(炔诺酮),17β-羟基-17α-乙炔基-雄甾-4-烯-3-酮(妊娠素)和17a-羟基孕甾-4-烯-3,20二酮(17α-羟基黄体酮)为原料,经NaBH,还原、脱水、双键转位和酯化等反应合成一系列3,5-甾二烯化合物,用¹HNMR和MS证明了它们的结构。动物筛选结果表明,17β-丙酰氧基-17α-乙炔基-雌甾-3,5-二烯(IV_b2有明显的抗早孕活性。中断早期妊娠的作用似与其雌激素活性有关。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

---

Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

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.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.