苯砜基乙酸酯类化合物对大型蚤的急性毒性效应以及定量结构活性相关分析

以大型蚤（Daphnia magna）为模型生物，测定了20种苯砜基乙酸酯类化合物在静态实验系统中的急性毒性效应，应用电荷模型方法对化合物的急性毒性进行定量结构-活性相关（QSAR）研究，结果表明，电荷方法建立的模型具有较高的预测能力（自由度校正的相关系数r^2adj=0.922），在所应用的诸多参数中，MW（分子量）、Qo(化合物中氧原子所带静电荷的平方值的和的平方根）、Q^2s（硫原子所带静电荷的平方值的和）三个参数的统计意义最为显著，对预测模型的分析可知，化合物中的基团-SO2-是活性中心，另外，两个含氧基团-NO2和-CO2-对化合物的活性也有较大的贡献。     

取代苯甲醛衍生物的定量结构—活性关系（QSAR）研究

本文研究了反应性化合物取代苯甲醛衍生物对大型蚤的４８ｈ急性毒性，建立了定量结构－活性关系模型，探讨了其毒性作用机制，发现其毒性主要取决于苯环上取代基的Ｈａｍｍｅｔｔ电效应常数。模预测结果与实验结果基本一致。     

有机磷酸酯类化合物的定量结构-活性关系及稳健性分析

应用理论线性溶剂化能关系（TLSER）模型研究了35种有机磷酸酯类（OP）化合物的结构及其对家蝇急性毒性之间的关系,得到了可以指示毒性作用机理的定量结构-活性关系．在OP化合物与生物体的作用过程中,分子的极性是影响活性的最重要因素,表明OP化合物可能与生物体发生特异性反应．采用Bootstrap方法分析模型的稳健性,结果表明,模型的系数、标准误差及相关系数均与Bootstrap估计接近,模型具有较强的稳健性．     

基于区间活性数据的定量结构-活性关系

利用贝叶斯统计方法构建了基于区间活性数据的取代苯胺和苯酚类化合物对大型溞(Daphniamagna)24 h急性毒性的定量结构-活性关系模型,并与基于平均数和中位数的点估计活性数据的定量结构-活性关系模型进行了比较.结果表明,前者可以充分利用化合物的活性数据信息,模型具有更好的拟合效果与预测能力以及较宽的应用范围.基于区间活性数据的定量结构-活性关系模型可为生态风险评价等提供更加可靠的预测数据.     

多溴二苯醚类化合物干扰人雌激素受体alpha活性机理的理论研究

基于分子对接方法探讨了多溴二苯醚(PBDEs)类化合物与人雌激素受体α亚型间的分子作用机理.对多溴二苯醚类化合物是否具有拟雌激素功能的研究得出:可通过对接打分值和化合物结构特征来推测PBDEs母体化合物是否具有拟雌激素活性;对HO-PBDEs,与氨基酸残基GLU53和/或ARG394形成氢键可能是影响其拟雌激素活性的重要因素;对MeO-PBDEs,疏水MeO-位于结合腔的疏水中部有利于拟雌激素活性.从结构及构象分析得出,邻位疏水基(Br-、MeO-)有利于PBDEs类化合物的拟雌激素活性.同时对多溴二苯醚类化合物是否具有抗雌激素功能的结合特征研究发现,表现出抗雌激素活性的部分PBDEs类化合物伸进通常被雌激素受体拮抗剂雷洛昔芬和4-羟基它莫西芬的烷基胺侧链占据的通道,而大多数未表现出抗雌激素活性的PBDEs类化合物的结合模式类似雌激素受体激动剂17β-雌二醇,位于结合腔,没有伸进通道.本研究从化合物结构及化合物在受体内结合的构象特征上解释化合物活性不同的原因,以期能够利用构象分析得到的结果进行筛选.     

葡萄属低聚茋清除超氧阴离子自由基作用的研究

利用化学发光法研究了葡萄属植物白藜芦醇及其低聚物对氧自由基作用的影响,并探讨了结构与活性之间的关系。结果提示葡萄属低聚芪具有良好的清除超氧阴离子自由基的能力,它的抗氧化能力与聚合度的大小和化合物中酚羟基的个数无必然的关系,而主要取决于化合物本来的结构。     

含硫苯衍生物对发光细菌的毒性效果及其定理结构活性相关分析

利用发光细菌法测定了２９种氯取代和硝苯取代的苯硫（砜、亚砜）基乙酸酯的毒性，通过定量结构活性相关（ＱＳＡＲ）分析发现：此类化合物的毒性主要与其取代基的电荷效应相关，电荷的区域分布对化合物的毒性效应有重要影响。推测该化合物的毒性机理是毒物分子与发光反应中的主要辅酶ＦＭＮＨ２形成了氢键。还发明：在这类链状毒物分子中，远离活性中心一端的基团具有脱毒作用。     

分子对接法研究多溴二苯醚衍生物与芳香化酶的作用机理

应用分子对接方法探讨了多溴二苯醚(PBDE)衍生物与人胎盘芳香化酶间的可能作用机理.通过分析对接生成的构象发现,羟基多溴二苯醚(HO-PBDEs)和甲氧基多溴二苯醚(Me O-PBDEs)与人胎盘芳香化酶间形成氢键的情况不同.对人胎盘芳香化酶有抑制活性的HO-PBDEs通过其羟基(—OH)与氨基酸残基Arg435、Arg115、Arg375、Asp309和Ala306形成氢键,而对人胎盘芳香化酶无抑制活性的Me O-PBDEs的甲氧基(Me O—)几乎不与芳香化酶内氨基酸残基形成氢键,这可能是二者对芳香化酶抑制活性不同的原因.由此推测,化合物作为氢键供体可能是多溴二苯醚衍生物具有抑制芳香化酶活性的结构基础.本研究从化合物结构及化合物与人胎盘芳香化酶结合的构象特征上解释化合物活性不同的原因,以期能够利用构象分析得到的结果进行筛选.     

雷公藤新的降倍半萜成分

从贵州产雷公藤（ＴｒｉｐｔｅｒｙｇｉｕｍｗｉｌｆｏｒｄｉＨｏｋＦ．）中分离得到８个化合物,其中一个为新的降倍半萜化合物雷公藤酮（１）,根据光谱（ＩＲ,１ＨＮＭＲ,１３ＣＮＭＲ,ＨＲＭＳ,ＣＤ等）数据分析并通过Ｘ射线晶体分析确定了结构;另外７个化合物分别鉴定为雷公藤素（２）,（±）６氧２（４′羟基３′,５′二甲氧苯基）３,７二氧杂二环［３．３．０］辛烷（３）,ｔｒｉｐｔｅｒｉｆｏｒｄｉｎ（４）,雷公藤内酯酮（５）,雷公藤内酯醇（６）,雷公藤内酯甲（７）和对乙氧基乙酰替苯胺（８）．其中,３和８均为首次从该植物中分离得到．用二维核磁共振谱对３的氢谱和碳谱进行了指定     

酚类化合物麻醉毒性的CoFMA研究

通过比较分子力场分析方法(CoMFA)建立酚类化合物对梨形四膜虫极性麻醉毒性(pT)的三维定量结构-活性相关(3D-QSAR)模型.基于训练集41个化合物建立了预测模型,10个化合物作为验证集(含模板分子).训练集的CoMFA模型显示立体场、静电场对麻醉毒性贡献依次为53.9％和46.1％.其交叉验证相关系数(R2cv...     

三维原子场全息作用矢量用于芳香类化合物的三维QSAR研究

采用新型的的三维原子场全息作用矢量(3D-HoVAIF)研究了200种芳香化合物的化学结构与其生物毒性的定量构效关系(QSAR).首先对芳香化合物进行了结构参数化表达,然后采用逐步回归(SMR)对变量进行筛选,建立了三维定量构效关系模型.其87个无氢键分子的模型和113个有氢键分子的模型的复相关系数和标准偏差分别为R2=0.801,SD=0.473和R2=0.929,SD=0.318.模型具有良好的稳定性和预测能力,证明了该三维原子场全息作用矢量在分子结构表征和生物毒性预测上的适用性.     

A model based on molecular structure descriptors for predicting mutagenicity of organic compounds

A model predictive of the potential mutagenicity of organic compounds was devised by relating mutagenicity data obtained in the Ames reversion test to molecular structure parameters describing their hydrophobic, topological, steric and electronic properties. These included second order valence molecular connectivity index, parachor, molar refraction and polarizability of electrons. A classification rule was calculated, by means of discriminant analysis, using a training set of 117 compounds of various chemical classes. There was agreement between experimental data and theoretical expectations for the majority of compounds (70.9%), with homogeneous figures among the different chemical classes under scrutiny. An exception was represented by halogenated aliphatics with up to 3 C atoms, the mutagenicity of which was poorly predicted by the structural analysis model.     

Electrophysiological responses and field attraction of the grey corn weevil, Tanymecus (Episomecus) dilaticollis Gyllenhal (Coleoptera: Curculionidae) to synthetic plant volatiles

The grey corn weevil, Tanymecus (Episomecus) dilaticollis, is an economically important polyphagous pest in Eastern and Central Europe. The present research is the first published electrophysiological study of olfactory sensitivity of adult T. dilaticollis to plant volatiles. The electrophysiological responses of male and female antennae were recorded to 20 synthetic volatile organic compounds (VOCs), previously identified to be released from the preferred host plants, maize and sunflower. Antennae of both sexes responded to a wide range of volatiles from different chemical classes: fatty acid derivatives, aromatic compounds and terpenoids. Two green leaf volatiles, (E)-2-hexen-1-ol and (Z)-3-hexen-1-ol, and one terpenoid, (±)-linalool, elicited the strongest electrophysiological responses by male and female antennae. Relatively high electrophysiological activity by T. dilaticollis antennae was also recorded to benzaldehyde, eugenol and caryophyllene. In the field, (E)-2-hexen-1-ol and (Z)-3-hexen-1-ol, when presented individually, caught significantly more male and female T. dilaticollis than unbaited controls. These compounds could be developed into an attractive trap for the detection and monitoring of T. dilaticollis.     

Synthesis and evaluation of antioxidant activities of some indole-2,3-dione derivatives and analogs

In the present study, a series of novel Schiff bases of isatin were synthesized by condensation of imesatin with different aromatic aldehydes. The imesatins were synthesized by reaction of isatin with p-phenylenediamine. The chemical structures of the synthesized compounds were confirmed by means of IR, 1H-NMR, 13C-NMR, mass spectroscopy, and elemental analysis. These compounds were screened for antioxidant activity by DPPH, nitric oxide and hydrogen peroxide radical scavenging activity. In all the methods, the compound 3-(4-(3,4,5-trimethoxy benzylideneamino)phenylimino) indoline-2-one (5d) showed highest antioxidant activity because of the presence of electron donating groups and the compound 3-(4-(4-nitrobenzylideneamino)phenylimino) indoline-2-one (5f) showed the least activity because of the presence of an electron withdrawing group.     

In vitro microbiological evaluation of novel 2-oxo-2H-chromene-3-carbaldehyde containing 1,3,4-thiadiazole moiety

4-(5-(Methylthio)-1,3,4-thiadiazol-2-ylamino)-2-oxo-2H-chromene-3-carbaldehyde (3) and 4-(5-(ethylthio)-1,3,4-thiadiazol-2-ylamino)-2-oxo-2H-chromene-3-carbaldehyde (4) were prepared. The structures of the newly synthesized compounds were characterized by infrared (IR), nuclear magnetic resonance (NMR) spectral data and elemental analysis. The synthesized compounds were screened in vitro for their antibacterial activities. The synthesized compounds demonstrated moderate antimicrobial activity.     

Screening of the marine actinomycetes with anti-complement activity and isolation of the active fractions北大核心CSCD

Studies on anti-complement agents are essential for the development of drugs to treat various diseases caused by excessive or abnormal activation of the complement system. However, studies on microbial-derived anti-complement agents are still very limited. The anti-complement activities of 42 marine-derived actinomycete strains isolated from the sediment samples collected from Xinghai Bay in Dalian were studied using the hemolysis method. In addition, the active fractions of the strain Streptomyces sp. DUT11 were separated by C18 and Sephadex LH-20 column chromatography, and the active compounds with anti-complement activity were identified. Streptomyces strains S187, M5, S088, M8, S063, DUT11 and MD16 showed good anti-complement activities upon being cultured in TSB medium, with the strain DUT11 showing the best anti-complement activity among these strains. When different fermentation media were tested, the highest anti-complement activity of DUT11 was observed in M33 fermentation medium. The anti-complement activity was 56.5% for the extract of supernatant and 60.8% for the extract of mycelia, respectively. Furthermore, three compounds with anti-complement activity were obtained from the active components, which were identified as 3-indolecarboxylic acid (1), p-hydroxy benzoic acid (2) and 2-pyrrolecarboxylic acid (3). These results demonstrated that marine-derived streptomycetes can be employed to produce active compounds with anti-complement activity. This study presents a new alternative for the utilization of marine actinomycetes and provides a basis for the exploration of new anti-complement agents. © 2018 Science Press. All rights reserved.     

Antipredator activity and endogenous biosynthesis of defensive secretion in larval and pupal Delphastus catalinae (Horn) (Coleoptera: Coccinellidae)

Delphastus catalinae (Horn) is a predatory ladybird beetle (Coccinellidae) commonly used as a biocontrol agent against greenhouse infestation by whiteflies. It belongs to the basal subfamily Microweisinae, a group for which chemical defenses have not been previously investigated. The larval and pupal stages of D. catalinae possess minute secretory hairs that produce droplets containing compounds of both isoprenoid and polyketide origin. Bioassays with the predatory ant Crematogaster lineolata showed both the larval and pupal secretions to be deterrent. Moreover, isolated secretion components, from both classes of compounds, displayed antipredator activity against the ant. Experiments with D. catalinae larvae fed isotopically labeled glucose showed ¹³C-incorporation into both categories of compounds within the pupal secretion, demonstrating that these antipredator compounds, which differ from the typical nitrogenous defensive molecules of coccinellids, are biosynthesized endogenously. This suggests that the wide use of alkaloids by more derived coccinellids may have arisen after their divergence from the more basal Microweisinae.     

Human dietary intake and hazard characterization for residues of neonicotinoides and organophosphorus pesticides in Egyptian honey

In two recently published reports, hazards posed by dietary exposure to organophosphate and neonicotinoid plant protection products on the European honey bee (Apis mellifera L.) in Egypt were investigated. Using concentrations reported in those studies, an assessment of hazards posed by these two classes of insecticides to humans due to consumption of Egyptian honey from the Nile Delta during both spring and summer was performed. Twenty-eight compounds including metabolites were assessed for exposure of adult Egyptians based on the best- and worst-case scenarios. Even for the worst-case scenario, exposure to these two classes of pesticides in honey was 15-fold less than hazard index value of 1.0 for adverse effects on humans. Based upon this analysis, people exposed to these insecticides through consumption of honey products would be unlikely to exhibit adverse health outcomes.     

Störungen der Entwicklung und Funktion des männlichen Reproduktionssystems

Various recently published studies indicate increases in disorders of development and function of the male reproductive system during the last decades. This refers to reports on a decline in sperm count and increased incidences of testicular cancer, cryptorchidism and hypospadias. While the results of studies on the increase in (geographically varying) incidences of testicular cancer are unequivocal, data on changes in rates of cryptorchidism and hypospadias are rather limited. Meanwhile, numerous retrospective studies on changes in sperm concentrations in the ejaculate of normal men have been published. However, at present it is not possible to draw generally valid conclusions since results from some countries or geographic regions indicate a significant decline while in others either no changes or even slight increases have been reported. According to the so-called “Estrogen hypothesis”, the common cause of these disorders shall be an increased prenatal exposure to estrogens. Concerning exogenous estrogens, synthetic estrogens, phyto and mycoestrogens, and chemicals with estrogenic activity could play a role. A search in the available literature has revealed that at present more than 100 chemical compounds from different classes are known to possess estrogenic activity. This, however, is not the only way in which chemicals may be endocrinically active. Ubiquitously distributed compounds from the classes of polychlorinated dibenzodioxins/furans and biphenyls exhibit an antiestrogenic potential, while chemicals like p,p′-DDE, Linuron and Vinclozolin being competitive androgen receptor antagonists may act as antiandrogens. Concerning the very limited current knowledge, the estrogen hypothesis at present only represents an interesting basis for discussion. Most questions that would have to be answered in order to accept, reject or modify tis hypothesis are either completely open or only partially understood. Thus, there is an urgent need to initiate research efforts to clarify the toxicological significance for ecosystems and humans of chemicals with endocrine activity.     

沉积物毒性鉴别评估技术在一个有着多重污染物输入地点的应用

沉积物毒性鉴别评估用于确定造成沉积物整体毒性测试中观察到有害效果的原因。然而在多污染物的情况下,将总体毒性划分为为不同个体污染物单独造成的毒性的方法存在很多问题。利用一个有着多重输入与相关污染物的站点数据,我们为毒性鉴别评估提出一种通过追踪毒性单位（TUs）来确定是否囊括全部毒性的方法。首先确定出沉积物整体的毒性水平,然后将毒性来源划分至几种污染物大类,例如氨类,金属,非极性有机物等。本文中毒性很大程度上来源于非极性有机物,所以在萃取沉积物之后,将萃取物重新加回稀释水中以检测毒性的复原。每一部分污染物的毒性占比由溶剂梯度测量,并进行毒性检测。目标占比由气相色谱-质谱分析得到,从而鉴定出与特定成分相关的毒性。之后对这些成分相关的毒性单位进行测定以确定可能的原因组合和是否已囊括全部毒性。数据表明毒性既与已有化合物相关,又与新兴污染物相关,而两种污染物对于总体毒性的具体贡献则随实验地点改变。
精选自Howard C. Bailey, Catherine A. Curran, Peter Arth, Bonnie P. Lo, Rich Gossett. Application of Sediment Toxicity Identification Evaluation Techniques to a Site with Multiple-Contaminants. Environmental Toxicology and Chemistry: Volume 35, Issue 10, pages 2456–2465, October 2016. DOI: 10.1002/etc.3488
详情请见http://onlinelibrary.wiley.com/doi/10.1002/etc.3488/full