基于β-苯基萘型化合物的合成及其抗肿瘤活性的初步筛选

目的 合成新的β-苯基萘型平面产物,并初步筛选其抗肿瘤活性.方法 过渡金属催化合成N-N键亚胺叶立德,并进行1,3-偶极环加成形成共平面产物.结果 合成了吲唑[2.3-a]喹啉,收率中等.结论 筛选显示,产物1Ob具有抑制人肝癌BEL-7402瘤株的活性.     

戊二酰亚胺类抗生素的研究进展*

戊二酰亚胺娄抗生素从链霉菌发酵液提取分离得到,具有抗真菌、抗细菌、抗原虫、抗病毒、抗肿瘤及免疫抑制等多种生物活性。本类抗生素包括具有经过多年发展的环己酰亚胺、S-632类以及斩近发现的具有明显抑制肿瘤细胞迁移的大环内酯结构的migrastatin家族等。现对戊二酰亚胺类抗生素及其类似物的结构、活性和构效关系进行综述,并简单介绍了几个非微生物来源及化学合成的酰亚胺类物质。     

取代萘苄胺类化合物的合成及抗真菌活性

报道１８个Ｎ－甲基－Ｎ－（ｍ,ｐ－取代苄基）－α－取代萘苄胺类化合物的合成及抗真菌活性。抑菌测试结果表明：目标化合物对常见８种致病真菌均有不同程度的抑制活性,对浅表真菌活性好于深部真菌,与萘替芬相当,优于克霉唑,低于布替萘芬。化合物（７）,（８）,（１３）,（１４）等对Ｓ．ｘｃｈｅｎｃｋｉｉ活性是萘替芬及克霉唑的３０￣６０倍,化合物（２）,（７）,（８）,（１４）对Ｅ．ｆｌｏｃｃｏｓｕｍ的活性是萘     

戊二酰亚胺类抗生素S632最新研究进展

戊二酰亚胺类抗生素是由链霉菌产生的一类结构中含有酰亚胺环、具有多种生物学活性的微生物产物。近年来发现戊二酰亚胺类新抗生素S632具有显著的抗病毒、抗肿瘤、保护神经元等多种生物学活性,表明该类抗生素具有重要的理论研究价值和开发应用前景。文中从以下几个方面综述了抗生素S632的最新研究现状及进展,包括分子结构与理化性质、含量测定方法及内控质量标准、多种生物学活性(抗病毒、抗肿瘤、神经元保护作用、炎症反应的抑制作用),同时对S632的构效关系及其作用机制也进行了探讨。     

曲安萘德治疗口腔扁平苔癣的疗效时间相关性研究

目的观察曲安萘德治疗糜烂口腔扁平苔癣的疗效,并初步确定其疗效持续的具体时间。方法曲安萘德局部注射治疗口腔扁平苔癣治疗后3月、6月时评价治疗效果,对比分析两个时间段的疗效差别采用sas6.12统计软件对所得数据进行χ2检验,以P〈0.05为差异有显著差异。结果 3月后疗效显效6例（6.25%）、有效84例（87.50%）,有效率为93.75%,6月后疗效显效2例（2.08%）、有效26例（27.08%）,有效率为29.16%,两个时间段的疗效有统计学差异（P〈0.05）。结论曲安萘德局部注射治疗口腔扁平苔癣,治疗时间间隔以3月较好。     

萘骈苯骈吡喃酮类活性化合物研究进展

萘骈苯骈吡喃酮是一类由萘环和苯环分别在α,β-和γ,δ-稠合的六元不饱和内酯类化合物,多数与糖形成C-苷或O-苷;此类化合物具有良好的细胞毒或抗菌活性。迄今为止,报道了49个此类化合物,涉及26篇文献。本文综述了这49个萘骈苯骈吡喃酮类化合物的结构、生物和化学来源及其生物活性。表明链霉菌是萘骈苯骈吡喃酮类化合物的主要来源,已从链霉菌的次生代谢产物中分离鉴定了31个天然的萘骈苯骈吡喃酮类化合物;其良好的生物活性吸引化学家对其进行结构修饰和改造,得到了18个化学衍生物,其中1个已进入治疗乳腺癌的II期临床研究;萘骈苯骈吡喃酮可能是一类重要的抗肿瘤或抗菌药物先导化合物。     

新型PI3K抑制剂邻苯二甲酰亚胺及其衍生物的设计合成与抗肿瘤活性

目的设计合成新的磷脂酰肌醇3-激酶抑制剂,并测定其体外活性。方法通过结构替换、分子对接技术设计一系列邻苯二甲酰亚胺类化合物。以4-溴邻苯二甲酸酐为原料经胺解反应得到N-芳基-4-溴邻苯二甲酰亚胺Ⅰ1～Ⅰ8;Ⅰ1～Ⅰ8再与3-(4-氟苯磺酰胺基)苯硼酸经Suzuki偶联得到N-芳基-4-(3-对氟苯磺酰胺苯基)邻苯二甲酰亚胺Ⅲ1～Ⅲ8;以阿霉素为阳性对照,采用MTT法进行体外活性测定。结果与结论合成了16个未见文献报道的邻苯二甲酰亚胺类化合物,目标化合物的结构经1H-NMR、MS谱确证;体外活性实验结果显示,N-芳基-4-(3-对氟苯磺酰胺苯基)邻苯二甲酰亚胺衍生物具有潜在的抑制肿瘤生长作用,其中,化合物Ⅲ1对A549、MCF-7肿瘤细胞表现出显著的抑制活性,具有进一步研究的价值。     

高效液相色谱法测定软膏中曲安萘德和水杨酸含量

目的：建立一种快速的用高效液相色谱法测定曲安萘德（ＴＡ）和水杨酸（ＳＡ）的含量。方法：使用Ｃ１８色谱柱,流动相为甲醇∶水（６０∶４０Ｖ／Ｖ）,检测波长为２４０ｎｍ及２９０ｎｍ。结果：方法在７ｍｉｎ内完成测定,其中水杨酸在８～２４μｇ·ｍｌ－１浓度范围内,ｒ＝０．９９９５,ＲＳＤ＝０．４９％,回收率为９９．７％～１００．３％;曲安萘德在６．２５～５０μｇ·ｍｌ－１浓度范围内,ｒ＝０．９９９８,ＲＳＤ＝０．４７％,回收率为９９．４％～９９．８％。结论：方法可行快速准确地检测软膏中的曲安萘德和水杨酸含量     

布地萘德联合福莫特罗吸入治疗支气管哮喘的临床价值分析

目的为了进一步提高我院治疗支气管哮喘的临床疗效,帮助患者早期恢复健康,本文就布地萘德联合福莫特罗吸入治疗支气管哮喘的临床价值进行了浅显的研究和探讨。方法将我院自2012年9月至2013年9月期间收治的154例支气管哮喘患者平均分为对照组（n=77）和观察组（n=77）,分别予以布地萘德单纯治疗和布地萘德联合福莫特罗吸入治疗,对两组患者用药后病情的变化情况、肺功能改善情况以及并发症发生情况进行观察和统计。结果观察组患者治疗的显效率和总有效率明显高于对照组患者（P〈0．05）;观察组患者肺功能的改善程度明显优于对照组患者（P〈0．05）;观察组观察组并发症发生率明显低于对照组患者（P〈0．05）。结论布地茶德联合福莫特罗吸入治疗应用于支气管哮喘治疗的效果十分显著,有效提高了治疗成功半,改善了患者的生活质量,值得推广。     

抗癌药Enzastaurin

蛋白激酶C（PKC）的过度表达与多种癌症相关，其中PKCβ与血管内皮生长因子（VEGF）诱导的肿瘤发展、血管生成密切关联。Enzastaurin（LY-317615）是由美国礼来公司开发的一种双吲哚马来酰亚胺类抗癌药，能选择性地抑制PKCβ。在多种临床前动物模型中显示出强效的抗肿瘤活性，在治疗晚期癌症病人的临床试验中也获得了较好的效果。     

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.     

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.