新型肟醚化合物杀叶蝉活性的CoMFA研究

用比较分子力场分析(CoMFA)方法对28个间苯氧基苄醇肟醚和30个联苯苄醇肟醚化合物杀叶蝉Nephotettix cincticeps活性的定量构效关系进行了研究。分别研究了上述两类化合物及其综合的QSAR模型,3种QSAR模型都表明肟苯环对位取代基是影响化合物杀叶蝉活性的主要因素,其体积和电性增加有利于提高化合物的杀叶蝉活性。比较3种模型,还发现综合模型为最佳预测模型,其交叉验证系数R2cv=0.628,非交叉验证的相关系数R2=0.971,标准偏差SE=0.109,F=133.84。用此模型预测了检验组10个化合物的 -lgLC50,结果满意。所得QSAR模型可为进一步合成更高活性的化合物提供指导。     

靶向乙酰胆碱酯酶和几丁质合成酶杀虫剂衍生化合物三维定量构效关系模型构建

为获得活性更佳且同时具备苯甲酰基脲类和氨基甲酸酯类活性的新型双靶标杀虫剂——N-氯磺基-N-甲基氨基甲酸酯衍生物,构建此类化合物的三维定量构效关系（three-dimensional quantitative structure-activity relationship,3D-QSAR）模型,以18种具有双靶标活性的N-氯磺基-N-甲基氨基甲酸酯衍生物为训练集,分别采用比较分子力场分析（comparative molecular field analysis,CoMFA）法和比较分子相似性指数分析（comparative molecular similarity index analysis,CoMSIA）法进行3D-QSAR模型的构建,基于3D-QSAR模型分析同一骨架取代基的变化带给化合物的活性变化,预测不同力场对化合物活性的影响,并对设计的衍生化合物进行活性预测分析。结果表明,经CoMFA法和CoMSIA法构建的3D-QSAR模型可信度高（交叉验证系数q²分别为0.728和0.563）,且有良好的活性预测能力（非交叉验证系数r²分别为0.954和0.981）。基于该模型得到的化合物预测活性与实际活性残差较小且存在良好的线性关系,进一步证明所得3D-QSAR模型的可靠性。通过分析3D-QSAR模型的力场分布,推测在R¹基团处引入位阻较大的疏水性基团、在R²基团苯环的邻位引入同时具有负电性和疏水性但不含卤素原子的基团、用负电性的大位阻基团取代R基团等均可提高N-氯磺基-N-甲基氨基甲酸酯的活性。基于此设计的20种衍生化合物的活性变化从正反两方面印证了该推测的合理性。研究成果可用于指导兼具苯甲酰基脲类和氨基甲酸酯类杀虫剂作用机制的N-氯磺基-N-甲基氨基甲酸酯衍生物的设计。     

吡啶甲基亚氨基噻(噁)唑烷的合成及生物活性

根据天然海藻糖酶抑制剂的结构设计了一类吡啶甲基亚氨基噻(噁)唑烷化合物, 通过吡啶甲基异硫氰酸酯和相应的胺反应, 然后在盐酸或黄色氧化汞条件下关环,合成了吡啶甲基亚氨基噻唑烷和噁唑烷,其结构得到IR、1H NMR、HRMS的确证。测试了化合物对昆虫(家蝇)飞行的抑制能力。对影响合成反应的因素以及生测结果进行了讨论。     

杀菌剂啶菌噁唑的高效液相色谱分析

建立了一种用反相高效液相色谱测定啶菌噁唑的定量分析方法。采用C18ODS色谱柱,以甲醇-水(75∶25,体积比)作为流动相,流速1.0mL/m in,检测波长220nm。啶菌噁唑色谱图显示两个吸收峰,分别为两个同分异构体Z体和E体。在400700μg/mL浓度范围内,标准溶液浓度和吸收峰面积之间有良好的线性关系,回归方程为Y=4.846 7x+232.85,相关系数r为0.999 2;对原药溶液及其制剂溶液测定的重复性SR分别为0.004 0和0.004 7。该方法准确、精密,适用于啶菌噁唑的定量分析。     

抗性和敏感生物型菵草代谢精噁唑禾草灵的速度差异

为了测定菵草抗性生物型SD-04-SS和敏感生物型SD-12对精噁唑禾草灵代谢速度的差异,建立了精噁唑禾草灵及其主要代谢产物精噁唑禾草酸、6-氯苯并噁唑酮的高效液相色谱(HPLC)分析方法。结果表明,在0.123~30.000μg/m L范围内、0.977~1 000.000μg/m L范围内、0.469~30.000μg/m L范围内6-氯苯并噁唑酮、精噁唑禾草酸、精噁唑禾草灵浓度与响应值线性关系良好,相关系数(r)分别为0.991 2、0.972 2、0.996 3。应用上述方法分析发现,精噁唑禾草灵处理后2 h在菵草体内即可检测到精噁唑禾草酸和6-氯苯并噁唑酮,药后2~96 h抗性生物型SD-04-SS体内精噁唑禾草灵的含量始终略高于敏感生物型SD-12,药后24~72 h抗性生物型SD-04-SS体内精噁唑禾草酸的含量显著低于敏感生物型SD-12,说明抗性生物型降解精噁唑禾草酸的速度比敏感生物型更快。     

新型茉莉酸类植物生长调节剂的QSAR研究

应用 Cerius2 软件中的遗传函数算法(GFA)和分子力场分析方法(MFA)对18个新型茉莉酸类化合物具有的对大麦和番茄的生物活性进行定量构效关系(QSAR)研究,所建模型都通过了显著性检验,交叉验证系数r2CV均大于0.810,表明模型都具有良好的预测可靠性。计算研究表明: 分子的热力学性质 (各种原子类型 AlogP 描述符)、空间结构状态(Jurs-RPSA参数)、 电性描述符(Dipole-mag 和 HOMO)和结构描述符(Hond Acceptor)是影响活性的主要二维因素。用三维QSAR方法研究了茉莉酸类化合物与其受体有效相互作用时所需的理化特征,并进一步验证了二维QSAR模型的可靠性。该研究可为进一步了解茉莉酸类化合物在植物体内的信号传导机制和研制具有生态农药性质的茉莉酸类植物生长调节剂提供理论指导。     

稻稗对噁唑酰草胺的非靶标抗药性和对氰氟草酯的交互抗药性

为明确稻稗对噁唑酰草胺的非靶标抗药性和对氰氟草酯的交互抗药性水平,通过剂量反应试验测定辽宁新民(R_1)、黑龙江虎林(R_2)和黑龙江哈尔滨(R_3)3个稻稗种群对噁唑酰草胺的非靶标抗药性和对氰氟草酯的交互抗药性水平。结果显示,R_1、R_2、R_3在喷施细胞色素P450抑制剂杀草强后对噁唑酰草胺的抗性指数比分别为1.14、1.71、2.38,表明R_1对噁唑酰草胺的抗药性与非靶标P450的活性无关,R_2和R_3对噁唑酰草胺的抗药性可能是靶标与非靶标的共同作用。3个稻稗种群对氰氟草酯的抗性指数分别为25.73、12.79、10.29,表明3个稻稗种群都对氰氟草酯产生了交互抗药性。     

噁唑菌酮与精甲霜灵复配对葡萄霜霉病的防效及药剂在葡萄中的残留

为明确噁唑菌酮与精甲霜灵复配在防治葡萄霜霉病上的可行性及安全性,对噁唑菌酮与精甲霜灵进行了室内联合毒力测定、田间药效及残留试验.结果表明:噁唑菌酮与精甲霜灵按质量比1:1复配,对葡萄霜霉病的联合毒力表现为增效作用,EC50值为2.52 mg/L,共毒系数(CTC)为154.53.30％ 噁唑菌酮 ? 精甲霜灵悬浮剂(噁...     

2-取代苯基-5-取代苯甲酰胺基-1,3,4-噻二唑的合成、抑菌活性及三维定量构效关系

以取代苯甲酸为起始原料，与氨基硫脲、三氯氧磷及取代苯甲酰氯进行缩合，制备了33个2-取代苯基-5-取代苯甲酰胺基-1,3,4-噻二唑 E ₁ ~E ₃₃ 。采用核磁共振氢谱 (1H NMR) 和高分辨质谱 (HRMS) 等对目标化合物的结构进行了确证及表征。采用菌丝生长速率法测定了目标化合物对根霉Rhizopus nigricans、青霉Penicillium glaucum、灰霉Botrytis cinerea、交链孢霉Alternaria brassicae和黑曲霉Aspergillus niger的体外抑菌活性。针对黑曲霉的抑制活性，分别利用CoMFA和CoMSIA对目标化合物进行了初步的三维定量构效关系 (3D-QSAR) 研究。结果表明，大部分化合物表现出良好的抑菌活性，在50 μg/mL下，化合物 E ₁ 、 E ₂ 和 E ₂₉ 对供试真菌的抑制率均达到80%以上，与对照药剂百菌清和多菌灵的抑菌效果相当。综合两种模型的结果，发现静电场的贡献值高于其他势场，且当苯环a的4位引入供电子基、苯环a的2位和6位以及苯环b上引入吸电子基时，有利于化合物抑菌活性的提高，可为进一步指导设计合成此类高活性化合物提供理论依据。     

N-(5-芳基-1,3,4-噁二唑-2-基)-N′-4-氟苯氧乙酰基硫脲的合成及抑菌活性

为了寻找更好的具有生物活性的化合物,从4-氟苯氧乙酸出发先合成酰基异硫氰酸酯,再与2-氨基-5-芳基-1,3,4-噁二唑反应合成了10个新的酰基硫脲类化合物,其结构经红外光谱、核磁共振氢谱、质谱和元素分析确认。采用平皿培养菌落生长速率法对6种病原菌进行了初步的生物活性测试,结果表明,在50mg/L浓度下,大部分化合物对黄瓜灰霉病菌Botrytis cinereapers、小麦赤霉病菌G ibberella zeae的抑制率达60%以上,其中Ⅱa、Ⅱc两个化合物对小麦赤霉病菌的抑制率达90%以上。     

Ligand-based computer-aided pesticide design. A review of applications of the CoMFA and CoMSIA methodologies

An overview is given of the CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methodologies that are established ligand-based molecular design tools widely used by medicinal and pesticide chemists. In the absence of a three-dimensional structure of the target biopolymer, CoMFA and CoMSIA often provide a practical solution to an otherwise intractable problem of proper characterization of ligand-receptor interactions. These techniques are especially important in agrochemistry, where the number of known molecular structures of pesticide targets is limited. The use of CoMFA and CoMSIA in the agrochemical field for modelling the interactions of insecticides, fungicides, herbicides and herbicide safeners with their target binding sites is illustrated by using some selected published work. The CoMFA and CoMSIA models developed have been used successfully to map the properties of unknown receptors, construct hypotheses for ligand-receptor interactions, optimize lead structures, design novel active compounds, and predict biological activities. The application of CoMFA by the present authors for deriving a binding site hypothesis for dichloroacetamide-type herbicide safeners is described in somewhat more detail.     

3-二氯乙酰基-2,5-二甲基-2-乙基-1,3-噁唑烷减轻氯磺隆对玉米的伤害作用研究

采用室内生物测定方法,测定了玉米主根长、根鲜重、芽长、芽鲜重,研究了除草剂安全剂3-二氯乙酰基-2,5-二甲基-2-乙基-1,3-噁唑烷减轻氯磺隆对玉米的伤害作用。试验结果表明:当安全剂3-二氯乙酰基-2,5-二甲基-2-乙基-1,3-噁唑烷与除草剂氯磺隆的浓度比为5∶1时,对玉米由1μg/kg的氯磺隆伤害有较好的解毒效果,保护率可达60%～110%。     

Modelling the effects of sub-lethal doses of herbicide and nitrogen fertilizer on crop–weed competition

The effects of sub‐lethal dose of herbicide and nitrogen fertilizer on crop–weed competition were investigated. Biomass increases of winter wheat and a model weed, Brassica napus, at no‐herbicide treatment with increasing nitrogen were successfully described by the inverse quadratic model and the linear model respectively. Increases in weed competitivity (β₀) of the rectangular hyperbola and parameter B in the dose–response curve for weed biomass, with increasing nitrogen were also successfully described by the exponential model. New models were developed by incorporating inverse quadratic and exponential models into the combined rectangular hyperbola with the standard dose–response curve for winter wheat biomass yield and the combined standard dose—response model with the rectangular hyperbola for weed biomass, to describe the complex effects of herbicide and nitrogen on crop–weed competition. The models developed were used to predict crop yield and weed biomass and to estimate the herbicide doses required to restrict crop yield loss caused by weeds and weed biomass production to an acceptable level at a range of nitrogen levels. The model for crop yield was further modified to estimate the herbicide dose and nitrogen level to achieve a target crop biomass yield. For the target crop biomass yield of 1200 g m^?2 with an infestation of 100 B. napus plants m^?2, the model recommended various options for nitrogen and herbicide combinations: 140 and 2.9, 180 and 0.9 and 360 kg ha^?1 and 1.7 g a.i. ha^?1 of nitrogen and metsulfuron‐methyl respectively.     

Three-dimensional common-feature hypotheses of inhibitors of calling behaviour and in vitro [14C]acetate incorporation by pheromone glands of Plodia interpunctella

Some octopamine (OA) agonists were found to suppress the calling behaviour and pheromone biosynthesis in vitro of the Indian meal moth, Plodia interpunctella (Hübner), a stored-product pest. Compounds were screened using a calling behaviour bioassay of female P interpunctella. Three active derivatives, with activity at the nanomolar level, were identified. In order of decreasing pheromonostatic activity these were: 2-(2-ethyl-6-methylanilino)oxazolidine > 2-(2,6-diethylanilino)thiazolidine > 2-(2,6-diethylanilino)oxazolidine. These compounds showed also in vitro inhibitory activities in de novo pheromone biosynthesis. Three-dimensional pharmacophore hypotheses were built from a set of 19 compounds. Among the ten common-featured models generated by the program Catalyst/HipHop, a hypothesis including a ring aromatic group (RA), a positive ionizable group (PI) and two hydrophobic aliphatic (HpA1) features was considered to be essential for inhibitory activity in the calling behaviour and pheromone biosynthesis in vitro. Active compounds mapped well onto all the RA, PI and HpA1 features of the hypothesis. Less-active compounds were shown not to achieve the energetically favourable conformation which was found in the active molecules in order to fit the 3-D common-feature pharmacophore models. The present studies demonstrate that inhibition of calling behaviour and PBAN-stimulated incorporation of radioactivity is by OA-agonistic activity.     

1,3-氮硫杂环化合物防治芦笋茎枯病的QSAR研究

用比较分子力场分析(CoMFA)方法对三小类1,3-氮硫杂环化合物防治芦笋茎枯病的定量构效关系进行了研究。分别研究了每一小类及综合的QSAR模型,发现对于各小类,苯环上取代基的变化影响其活性,从整体来看,影响活性的因素则集中在杂环上。所得的QSAR模型为进一步合成更高活性的化合物提供了指导。