盘花垂头菊中两种新型倍半萜类化合物抑制人肝癌SMMC-7721细胞生长

1β ,8 二当归酰氧基 2 β 己酰氧基 3β ,10 二羟基 4α 氯 11 甲氧基 没药 7(14) 烯 (化合物 1)和 1β ,8 二当归酰氧基 2 β 己酰氧基 3β 羟基 4α 氯 10 ,11 二氧代 异亚丙基 没药 7(14) 烯 (化合物 2 )是从盘花垂头菊 (ＣｒｅｍａｎｔｈｏｄｉｕｍｄｉｓｃｏｉｄｅｕｍＭａｘｉｍ )中提取出来的[1] 高含氧的甜没药烯型倍半萜 (ｈｉｇｈｌｙｏｘｙｇｅｎａｔｅｄｂｉｓａｂｏｌａｎｃｅｓｅｓｑｕｉｔｅｒｐｅｎｅｓ ,ＨＯＢＳ)化合物 ,其结构式分别为 :　　盘花垂头菊是多年生草本植物 ,在我国主要分布于青…     

具有抗炎活性的双三糖链呋甾皂苷的合成

目的设计合成两个甲基原薯蓣皂苷的衍生物，分别为3，26-O-二{α-L-吡喃鼠李糖基-（1→2）-[α-L-吡喃鼠李糖基-（1→4）]-3，6-O-二特戊酰基-β-D-吡喃葡萄糖基}-22-甲氧基-25（R）-呋甾-5-烯-3β，26-二醇（1）和3，26-O-二{α—L-吡喃鼠李糖基-（1→2）-[a—L-吡喃鼠李糖基-（1→4）]-β-D-吡喃葡萄糖基}-22-甲氧基-25（R）-呋甾-5-烯-3β，26-二醇（2）。方法以薯蓣皂素为起始原料，采用逐步糖苷化策略，经10步反应制得目标化合物，总收率约为15％。结果与结论合成的两个双三糖链呋甾皂苷均为未见文献报道的新化合物．其结构经ESI-MS和^13C-NMR确证，初步生物活性筛选结果表明化合物1具有一定的抗炎活性。     

4-取代17β-羟基在-7α-甲基-4-雌烯-3-酮的合成和抗生育活性

为了寻找抗生育药物,从17β-羟基-7α-甲基-4-雌烯-3-酮经17β-羟基-7α-甲基-4β,5β-环氧雌烷-3-酮合成了七个4-位取代的目标化合物:4,17β-二羟基-7α-甲基-4-雌烯-3-酮及其17-乙酸酯、4-甲氧基-17β-羟基-7α-甲基-4-雌烯-3-酮及其17-乙酸酯、4-氯-17β-羟基-7α-甲基-4-雌烯-3-酮及其17-乙酸酯和4-溴-17β-羟基-7α-甲基-4-雌烯-3-酮。这些化合物均可竞争性地与人蜕膜孕酮受体结合,并能抑制蜕膜细胞的发育,对大鼠具有显著的抗着床活性。     

萱草根化学成分的分离与结构鉴定

目的 研究萱草根的化学成分。方法 通过理化性质和光谱数据的分析鉴定了12个化合物的结构。结果与结论 自萱草根[Hemerocallis fulva(L.)L.]中分离得到12个化合物。分别鉴定为7-hydroxynaphthalide(1)，3α-乙酰基-11-氧代-12-乌苏烯-24-羧酸(2)，3-氧代羊毛甾-8，24-二烯-21-羧酸(3)，3β-羟基羊毛甾-8，24-二烯-21-羧酸(4)，3α-羟基羊毛甾-8，24-二烯-21-羧酸(5)，β-谷甾醇(6)，25(R)-螺甾烷-4-烯-3，12-二酮(7)，2’，4，6’-三羟基-4’-甲氧基-3’-甲基二氢查耳酮(8)，α-乳香酸(9)，β-乳香酸(10)，11α-羟基-3-已酰基-β-乳香酸(11)及脂肪族化合物(12)。除化合物1，6，8，12外其余均为首次从该属植物中分得。化合物2，9，10，11的^13C-NMR数据为首次报道。     

忍冬花蕾化学成分研究

目的：对忍冬花蕾化学成分进行研究，寻找抗菌活性化合物。方法：采用溶剂分配法，硅胶柱层析进行成分提取、分离。运用UV，IR，MS，^1H-NMR,^13C-NMR及标准品对照等。结合文献对比确定其结构，并进行抗菌活性药理实验。结果：从忍冬花蕾中分离得到11个化合物，分别是木犀草素（Ⅰ），5－羟基－7，3′，4′，5′－四甲氧基黄酮（Ⅱ）、5－羟基－7，3′，4′－三甲氧基黄酮（Ⅲ），5－羟基－7，4′－二甲基氧基黄酮（Ⅳ）、槲皮素（Ⅴ）、忍冬苷（Ⅵ）、5，7，3′，4′－四羟基黄酮醇－3－O－β-D－葡萄糖苷（Ⅶ）、3－O-[α-L－鼠李吡喃糖苷（1→2）－α－L－阿拉伯吡喃糖基]－28－O-[β-D-葡萄吡喃糖基（1→6）－β-D－葡萄吡喃糖基]齐墩果酸（Ⅷ）、绿原酸（Ⅸ）、胡萝卜苷（Ⅹ）、蔗糖（Ⅺ）。结论：化合物Ⅳ为首次从该属植物中发现，化合物Ⅴ，Ⅵ、Ⅷ和Ⅹ为首次从该植物的花蕾中发现，一些化合物显示较强的抗菌活性。     

长毛籽远志根的化学成分研究

为长毛籽远志Polygala wattersii的质量控制和进一步的开发提供科学依据,我们对它的根进行了系统的化学成分研究。利用砖胶、SephadexLH-20、制备薄层色谱及半制备液相等多种色谱分离技术进行分离和纯化,应用El—MS、ESI—MS、1HNMR及13CNMR等现代波谱技术并与文献相对照等方法鉴定化合物的结构。共从长毛籽远志根中分离鉴定了23个化合物,包括11个[口山]酮类：1,3-二羟基[口山]酮（1）,1-羟基-3-甲氧基[口山]酮（2）,1,3-羟基-2-甲氧基[口山]酮（3）,1,3,7-三羟基-2-甲氧基[口山]酮（4）,1,3,6-三羟基-2,7-二甲氧基[口山]酮（5）,1,6,7-三羟基-2,3-二甲氧基[口山]酮（6）,1,7-二羟基-2,3-亚甲二氧基[口山]酮（7）,1,7-二甲氧基[口山]酮（8）,1,2,3-三甲氧基[口山]酮（9）,1-甲氧基-2,3-亚甲二氧基[口山]酮（10）,6-羟基-1-甲氧基-2,3-亚甲二氧基[口山]酮（11）;9个糖酯类：3＇-O-阿魏酰基-6-O-乙酰蔗糖（12）,arillatose B（13）,sibficoseA5（14）,sibricoseA6（1S）,3＇,6-二-O-芥子酰基蔗糖（16）,tenufolisideA（17）,3＇-O-3,4,5-三甲氧基肉桂酰基-6—O-对甲氧基苯甲酰基蔗糖（18）,glomeratoseA（19）,1-O--对香甄酰基葡萄糖（20）;两个三萜皂苷类：bayogenin-3—O-glucoside（21）和tenufolin（22）及1个苯丙素类：芥了酸（23）。其中,化合物2和12为首次从远志属中分离得到,除化合物16外其它所有化合物均为首次从该种植物中分离得到。     

羟基胆烷酸类衍生物的抗癌活性研究Ⅱ．3β，5a，6β-三羟基胆甾烷-24-酸及3β，6β-二羟基胆甾-4-烯-24-酸衍生物的合成及其抗癌活性

目的探讨侧链极性的改变对氧代固醇类化合物抗癌活性的影响。方法以去氧猪胆酸为起始原料合成共22个(其中14个未见文献报道)侧链具一定极性、母环结构为3β，5a，6β-三羟基及3β，6β-二羟基-△^4-烯胆甾-24-酸衍生物，并以3β，5a，6β-三羟基胆甾烷(10)和3β，6β-二羟基胆甾-4-烯(11)为对照，比较其体外抗癌活性。结果与结论少部分化合物的抗癌活性比对照物稍强，大部分基本持平，少部分活性消失。希望从3β．5a，6β-三羟基及3β，6β-二羟基-△^4-烯胆甾-24-酸衍生物中找到比现有的氧代固醇抗癌活性更强的化合物的设想，目前尚未达到预期目的。     

4-取代17β-羟基在-7α-甲基-4-雌烯-3-酮的合成和抗生育活性

为了寻找抗生育药物,从17β-羟基-7α-甲基-4-雌烯-3-酮经17β-羟基-7α-甲基-4β,5β-环氧雌烷-3-酮合成了七个4-位取代的目标化合物:4,17β-二羟基-7α-甲基-4-雌烯-3-酮及其17-乙酸酯、4-甲氧基-17β-羟基-7α-甲基-4-雌烯-3-酮及其17-乙酸酯、4-氯-17β-羟基-7α-甲基-4-雌烯-3-酮及其17-乙酸酯和4-溴-17β-羟基-7α-甲基-4-雌烯-3-酮。这些化合物均可竞争性地与人蜕膜孕酮受体结合,并能抑制蜕膜细胞的发育,对大鼠具有显著的抗着床活性。     

侧茎垂头菊挥发油化学成分的探析

目的 为更好地开发以及利用侧茎垂头菊。方法 本文就侧茎垂头菊挥发油化学成分进行研究与分析,借助于水蒸汽蒸馏法来进行侧茎垂头菊所含挥发油的提取,利用GC毛细管柱来实施分析,并借助于归一化法对其相对含量进行测量,经气相色谱-质谱法的应用来鉴定侧茎垂头菊挥发油化学成分。结果 通过测量鉴定发现有60个化合物,其主要成分有1-乙烯基氧乙烷、4-甲基辛烷、丁内酯、β-月桂烯、5,5-二甲基-3-以丙烯基-环戊烯、1-甲基-3-[1-甲基乙基]-苯、1-乙烯基-3-乙基苯、1-甲基-4-[1-甲基乙烯基]-环乙烯、IS-[1-甲基-1-乙烯基-2,4-双[1-甲基乙烯基]-环乙烷、葵酸甲酯2,3,4,4a,5,6-六氢-1,4a-二甲基-7-[1-甲基乙烯]-萘、正十六烷酸、植醇、正二十七烷、6,10-二甲基-2-十二烷酮、十八烷、6-甲基-十八烷、1,3,3-三甲基-2-乙烯基-环乙烯、a-法呢烯、石竹烯氧化物、别香树烯氧化物、反式松香芹醇、正十二酸-2-苯乙酯、[E,E]-1,9-环十六碳二烯、1,2,3,5,6,7,8,8a-八氢-1,8a-二甲基-7-[1-甲基乙烯基]-萘、7,11-二甲基-3-亚甲基-1、a,a,4-三甲基-苯甲醇、6,10-十二碳三烯等。结论 通过对侧茎垂头菊挥发油化学成分中的60个化合物的研究分析,来更好地开发以及利用侧茎垂头菊。     

卷柏的化学成分

目的研究卷柏[Selaginella tamariscina(Beauv.)Spring]的化学成分。方法采用硅胶柱色谱、ODS柱色谱、制备型HPLC等手段进行分离纯化,并利用波谱学方法鉴定化合物的结构。结果从卷柏乙醇提取物中分离得到13个化合物,分别鉴定为3β-羟基-7α-甲氧基-24β-乙基-胆甾-5-烯(1)、胆甾醇(2)、β-谷甾醇(3)、海棠果酸(4)、白桦脂酸(5)、5,4′-二羟基-7-甲氧基黄酮(6)、3-methoxychrysazin(7)、穗花杉双黄酮(8)、异柳杉双黄酮(9)、香草酸(10)、对甲氧基苯甲醛(11)、对羟基苯甲酸(12)、胡萝卜苷(13)。结论化合物1-2、4-7、10、13为本属植物中首次分离得到的化合物。     

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.

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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.     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

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.