云南土壤真菌07—11号菌株中的活性成分

从云南土壤真菌07－11发酵液乙酸乙酯层浸膏中得到5个活性成分,经光谱数据分析和理化鉴别,分别鉴定为邻羟基苯甲酸（Ⅰ）、4,6－二羟基－5－甲基－1（3H）异苯骈呋喃酮（Ⅱ）、2－甲酰基－3,5－二羟基－4－甲基苯甲酸（Ⅲ）、N－（4－羟基－2－甲氧苯基）乙酰胺（Ⅳ）以及麦角甾－7,22－二烯－3,6－二酮（Ⅴ）,它们对稻瘟霉分生孢子及菌丝体都有一定抑制作用。其中化合物Ⅳ为首次分离得到的天然产物,其谱学数据也是首次报道。     

马山前胡化学成分研究

从广西特有的前胡属植物马山前胡Peucedanum mashanense Shan et Sheh根中首次分得10个化合物晶体，经理化常数和波谱解析，分别鉴定为3′(R)-( )-亥茅酚（1）、3′（S）－（－）－亥茅酚（2）、印度枸桔素（3）、石防风素（4）、珊瑚菜素（5）、水合氧化前胡素（6）、佛手柑内酯（7）、β－谷甾醇（8）、褐煤酸（9）和甘露醇（10），其中化合物1为一个新天然产物。     

1-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-3-(N-甲基-N-取代苄基氨基)-2-丙醇的合成及抗真菌活性研究

根据三唑类抗真菌药物作用靶酶－羊毛甾醇14α－去甲基化酶的三维晶体结构和药物与酶活性的位点的对接结果，设计合成了11个1－（1H－1，2，4－三唑－1－基）－2（2，4－二氟苯基）－3－（N－甲基－N－取代苄基氨基）－2－丙醇化合物，11个目标化合物均系首次报道，体外抗真菌活性试验结果表明，所有目标化合物对七种致病真菌都有不同程度的抗真菌活性，而且都比氟康唑的体外抗真菌活性好，化合物11的抗菌谱最广，抗真菌活性最高，对新型隐球菌，白色念珠菌，羊毛状小孢子菌和红色毛癣菌的抗菌活性比酮康唑高，有进一步开发的价值。化合物3，4，10也表现出较高的抗真菌活性。     

5—（4—羟基苯基）—1，3，4—恶二唑—2—硫酮的几种曼尼希碱的合成和生物活性

以对羟基苯甲酯乙酯为原料，经肼解、环化合成5－（4－羟基苯基）－1，3，4－恶二唑－2－硫酮，继而经Mannich反应合成了四种新曼尼希碱，其结构经红外光谱、核磁共振和元素分析证实。初步抑菌活性试验表明，显示弱的抑菌活性。     

灯盏花苷的全合成研究

目的 对治疗脑中风新天然活性成分灯盏花苷（1－O[3-(4H-吡喃酮）]6-O-咖啡酰基－β－D－吡喃葡萄糖苷（10）进行全合成研究。方法 由糠醇（1）合成了苷元3－羟基－4－吡喃酮（2），2与葡萄糖成苷后在无水条件下与经氯甲酸乙酯保护的咖啡酸在低温下对糖的6位羟基进行选择性酰化，再以氨－甲醇溶液脱除咖啡酰上的保护基。结果 该化合的的化学结构经红外，氢谱，碳谱，质谱鉴定，与天然产物完全一致。结论 以该合成方法能较高收率地得到目标化合物。     

连翘中一个新木脂素单糖甙

从连翘果实中分离得到了五个单体化合物，根据理化性质和光谱分析鉴定为：对－羟基苯乙酸[p-hydroxyphenyl acetic acid](1),( )松脂素－β-D－葡萄糖甙[( )pinoresinol-β-D-glucoside]（2），（＋）表松脂素－4－β-D-葡萄糖甙[( )epipinoresinol-4-β-D-glucoside]（3），（＋）松脂素单甲基醚－β-D-葡萄糖甙[( )pinoresinol mono methyl ether-β-D-glucoside]（4），连翘甙[phillyrin](5)。其中3未见文献报告，1－4为首次从连翘中分离得到的已知成分。     

中药路路通中的一个新三萜化合物

从中药路路通乙醇提取物中分得八个化合物，经光谱解析，相光化合物光谱对照及X－射线衍射确定其化学结构，其中化合物4鉴定为一新化合物，命名为3α－乙酰氧基－25－羟基－齐墩果酸，化合物3为首次从天然产物中分得，命名为3－酮基－12α－羟基－齐墩果－28，13β－内酯。     

17β-羟基-3-甲氧基雌甾-1,3,5(10),8-四烯-11-酮的14位差向异构体转化条件初探

目的：探讨17β-羟基－3－甲氧基雌甾－1，3，5（10），8－四烯－11－酮的14位差向异构体转化条件。方法：在不同酸性、碱性条件及不同温度下观察17β-羟基－3－甲氧基雌甾－1，3，5（10），8－四烯－11－酮的互变影响。结果：反应液酸碱性和反应温度与17β-羟基－3－甲氧基雌甾－1，3，5（10），8－四烯－11－酮互变有关。结论：在合成17β-羟基－3－甲氧基雌甾－1，3，5（10），8－四烯－11－酮中，应选择适当的反应条件，控制产物的异构化。     

抗菌药Tribactam关键中间体的合成

经7步反应合成了中间体2,设计并合成了手性（S）－2－甲氧基环己酮(6),并最后合成了tribactam的关键中间体（3S,4R）－3－[(R)-1（叔丁基二甲基硅氧基）乙基]4－{R)-2′-[（S）-6′-（2）′-甲氧基）－1′－氧代环己基]}－2－氮杂环丁酮（1）。合成路线短,收率高,成本低。     

HCMV蛋白酶抑制剂的研究(Ⅱ)杂环类抑制剂的设计与合成

目的 人巨细胞病毒（HCMV）是一种普遍存在的机会病原体。HCMV蛋白酶在装配蛋白产生和病毒壳体成熟中具有重要作用，抑制基作用可产生抗疱疹病毒药物。对杂环类HCMV蛋白酶抑制剂进行研究。方法 根据HCMV蛋白酶和拟肽类抑制剂复合物的晶体结构数据，借助计算机辅助药物设计手段，运用Docking(分子对接）技术，从MDDR库中筛选挑出35个预计可能与HCMV蛋白酶相互较好结合的杂环化合物。首先选择目标物2-（香豆素-3-基）-5-氟-4H-3,1-苯并恶嗪-4-酮（I）和3-（2-羟基-4-甲基-苯甲酰基）-2-（4-甲氧基-苯基）-2，3-二氢-异吲哚-1-酮（Ⅱ）为合成和检验对象。结果 设计并完成了目标物I和Ⅱ的合成路线。结论 所得产物的结构经MS，IR，^1H-NMR及元素分析确证与目标物I和Ⅱ相符。     

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.