杀虫剂分子靶标烟碱型乙酰胆碱受体研究进展

昆虫烟碱型乙酰胆碱受体(nicotinic acetylcholine receptors,nAChRs)广泛分布于昆虫中枢神经系统,是杀虫剂作用的主要靶标。目前昆虫中该受体的天然亚基组成尚不完全明确。果蝇的任意α亚基与脊椎动物的一个β亚基共表达是目前最好的异源表达模型,但仍然急需新的研究工具,研究表明一些与受体相关的蛋白质影响着表达。胞内磷酸化的调节作用为今后受体药理学特性的研究提供了新方向。受体亚基上一些关键氨基酸在新烟碱杀虫剂对受体的选择作用中起重要作用。在对吡虫啉抗性的褐飞虱种群中找到了与抗性相关的突变位点,这为新烟碱类杀虫剂靶标不敏感性研究提供了直接证据。对昆虫烟碱型乙酰胆碱受体的分子多样性、功能表达、胞内调节机制、受体与杀虫剂的选择作用及其抗性分子机理等的研究进展进行了综述。     

新烟碱类杀虫剂及稠环固定的顺式衍生物研究进展

新烟碱类杀虫剂是第四大类重要的杀虫剂,主要作用于昆虫的烟碱乙酰胆碱受体(nAChRs)。概述分析了新烟碱类杀虫剂的结构特征、作用机制及其构型,综述了近5年来新烟碱类杀虫剂的研究进展,并在比较分析的基础上,阶段性总结了作者近年来在稠环固定的顺式衍生物方面的研究工作。     

害虫对新烟碱类杀虫剂的抗药性及其治理策略

烟碱和新烟碱类杀虫剂都是作为后突触烟碱乙酰胆碱受体(nAChRs)的激动剂作用于昆虫中枢神经系统,但这两类杀虫剂存在明显不同的选择毒性:烟碱类对哺乳动物毒性较高,而杀虫活性低;新烟碱类具有高杀虫活性,而对哺乳动物低毒。由于新烟碱类杀虫剂的作用方式独特,对以前使用的如拟除虫菊酯类、氯化烃类、有机磷类和氨基甲酸酯类等杀虫剂很少或无交互抗性,该类杀虫剂为防治一些世界性重大害虫(包括对以前使用的杀虫剂具有长期抗性的害虫)作出了重要贡献。但现已发现不少害虫对新烟碱类杀虫剂产生了抗性。文章就害虫对新烟碱类杀虫剂的抗性概况、抗性机理和抗性治理策略进行了综述。     

烟粉虱成虫对不同单色光和光强度的趋性反应

目前,烟粉虱Bemisia tabaci已在我国大部分地区发生与为害,造成严重的经济和生态损失。当前,对其防治仍以化学防治为主,兼以利用天敌昆虫进行生物防治(张晓明等,2018)。但该类害虫已经对包括新烟碱类等多类杀虫剂产生了抗药性,这给烟粉虱的防治带来了巨大挑战(Wang et al.,2017)。     

新烟碱类杀虫剂对蜜蜂亚致死效应的研究进展

蜜蜂是一种经济型昆虫,其授粉作用在农业生产、濒临植物保护等方面具有重要意义。新烟碱类杀虫剂的广谱性、高效性、对哺乳动作的低毒性使得这类药剂备受人们关注,被广泛使用在农业生产生活中。近年来,新烟碱类杀虫剂对蜜蜂的潜在威胁也成为研究的热点,特别是对蜜蜂亚致死效应的研究。本文简要介绍了新烟碱类杀虫剂的应用概况及其作用机理,重点阐述了亚致死剂量的新烟碱类杀虫剂对蜜蜂生长发育及行为等的影响,并提出了几个有待进一步研究解决的问题,以期为我国新烟碱类杀虫剂对蜜蜂的安全性评价工作提供参考信息。     

新烟碱类杀虫剂毒理学研究进展

以吡虫啉和啶虫脒为代表的新烟碱类杀虫剂具有卓越的内肖活性及很高的残留活性。放射配基结合实验表明，新烟碱类杀虫剂对多种昆虫乙酰胆碱受体具有高亲和力，乙酰胆碱是其竞争性结合抑制剂，电生理学研究表明，该类杀虫剂与乙酰胆碱类似，可诱导瞬时内向电流，并可作用于药理学性质不同的昆虫烟碱型乙酰胆碱受体（nAChR)亚型，分子生物学研究进一步表明，该类杀虫剂主要作用于昆虫nAChRα亚基。     

新烟碱类杀虫剂的结构修饰及相关作用机制研究进展

新烟碱类化合物主要作用于昆虫的烟碱乙酰胆碱受体(nAChRs)。概述了新烟碱类杀虫剂的结构特征,阶段性地总结了近几年基于昆虫nAChRs结构,对新烟碱类化合物的杂环部分和功能基团进行结构修饰和改造的代表性研究成果,概要介绍了这些新化合物与昆虫nAChRs之间的相互作用机制,有助于进一步探索和开发高活性的新烟碱类化合物。     

USFWS计划终止新烟碱类农药在部分野生动物保护区内的使用

<正>新烟碱类农药对害蜂类及其他传粉昆虫造成了很大冲击,基于对此问题关注度的提高,美国鱼类与野生动物管理局(US Fish and Wildlife Service,USFWS)计划逐步停止新烟碱类农药在太平洋地域保护区内的使用。根据9月9日太平洋地域保护区首席Kevin Foerster签署的备忘录,USFWS的目标是让保护区管理者从2016年1月起不在以"任何农事理由"使用新烟碱类农药。该地域包括爱达荷州西北部、俄勒冈州、华盛顿州以及夏威夷和其他太平洋岛屿。Foerster先生在为保护区计划领导者的备忘录中写道:"尽管过渡时期会有一些灵活性,我     

新烟碱类杀虫剂的作用机制、应用及结构改造的研究进展

新烟碱类杀虫剂具有高效、低毒、广谱、选择毒性强和对环境安全等现代提倡的有机农药特点,是目前常用的最佳杀虫剂品种之一。本文结合最新进展,介绍了新烟碱类杀虫剂及其受体的结构特点、作用机制、应用及新烟碱类杀虫剂化合物分子结构改造等方面的研究。     

烟碱乙酰胆碱受体及其与新烟碱类相互作用的研究进展

对烟碱乙酰胆碱受体(nAChRs)的结构与功能、配体结合部位、门控机理以及与新烟碱类的相互作用进行了综述,并对nAChRs亚基基因突变和敲除对新烟碱类和多杀菌素敏感性的影响进行了讨论。nAChRs在脊椎动物和昆虫的胆碱能突触的快速神经传递中起着重要作用,其在昆虫中仅存在于中枢神经系统(CNS)中,而在脊椎动物中同时存在于CNS和神经肌肉连接处。nAChRs是新烟碱类杀虫剂、多杀菌素和杀螟丹的作用靶标。肌肉和CNS中的nAChRs是一个由两个α和三个非α(β,γ和δ)亚基组成的异数五聚体,该受体主要有三部分:一个在细胞外发现的区域(胞外区)、一个位于膜内的区域(跨膜区),另一个是位于细胞内的区域(胞质区)。每个亚基(从N-C端)都具有一个包含乙酰胆碱(ACh)结合部位的细胞外结构域;4个跨膜结构域(M1~4),其中M2的大部分氨基酸位于离子通道的内壁;一个胞质噜扑(loop)和一个胞外C端。通道门位于孔道内的疏水区。ACh结合部位位于天然和功能受体的两个亚基的界面,是由一个亚基的3个噜扑(A-C)和另一个亚基的3个噜扑(D-F)构成。每当受体与ACh(或其他激动剂)分子结合时,M2 α螺旋体的构象发生改变,使通道开启,处于阳离子传导状态,直至一个或两个激动剂分子从结合口袋解离,通道才关闭。如果激动剂一直存在,并反复结合,则通道处于脱敏状态。nAChRs与新烟碱类的各种选择性作用取决于新烟碱类的结构以及nAChRs的亚基组成。     

Neonicotinoids-from zero to hero in insecticide chemistry

In recent years, neonicotinoids have been the fastest-growing class of insecticides in modern crop protection, with widespread use against a broad spectrum of sucking and certain chewing pests. As potent agonists, they act selectively on insect nicotinic acetylcholine receptors, their molecular target site. The discovery of neonicotinoids can be considered as a milestone in insecticide research and facilitates greatly the understanding of the functional properties of insect nicotinic acetylcholine receptors. Because of the relatively low risk for non-target organisms and environment, the high target specificity of neonicotinoid insecticides and their versatility in application methods, this important class has to be maintained globally for integrated pest management strategies and insect resistance management programmes. This review comprehensively describes particularly the origin, structure and bonding as well as associated properties of neonicotinoid insecticides.     

Identifying the presence of neonicotinoidresistant peach-potato aphid (Myzus persicae) in the peach-growing regions of southern France and northern Spain

BACKGROUND: The neonicotinoid class of insecticides is a key component of pest management strategies used by stone fruit producers in Europe. Neonicotinoids are currently one of the most important tools for control of the peach‐potato aphid (Myzus persicae). Overreliance on neonicotinoids has led to the development of resistance through a combination of metabolic and target‐site resistance mechanisms in individual aphids. A resistance monitoring project was conducted by Syngenta in 2010 to determine the resistance status of M. persicae populations collected from France and Spain, and to determine the frequency of the target‐site mutation in those populations. RESULTS: Resistance monitoring suggests that resistance to neonicotinoids is relatively widespread in populations of M. persicae collected from peach orchards in the Languedoc‐Roussillon, Provence‐Alpes‐Cote d'Azur and Rhone‐Alpes regions of France, and resistance can be associated with the frequency of the target‐site mutation (R81T). The R81T mutation in its heterozygous form is also present in Spanish populations and is associated with neonicotinoid resistance. CONCLUSION: The widespread nature of neonicotinoid resistance in southern France and the potential for resistance development in northern Spain highlight the need for a coordinated management strategy employing insecticides with different modes of action to reduce the selection pressure with neonicotinoids. Copyright © 2011 Society of Chemical Industry     

Applied aspects of neonicotinoid uses in crop protection

Neonicotinoid insecticides comprise seven commercially marketed active ingredients: imidacloprid, acetamiprid, nitenpyram, thiamethoxam, thiacloprid, clothianidin and dinotefuran. The technical profiles and main differences between neonicotinoid insecticides, including their spectrum of efficacy, are described: use for vector control, systemic properties and versatile application forms, especially seed treatment. New formulations have been developed to optimize the bioavailability of neonicotinoids through improved rain fastness, better retention and spreading of the spray deposit on the leaf surface, combined with higher leaf penetration. Combined formulations with pyrethroids and other insecticides are also being developed with the aim of broadening the insecticidal spectrum of neonicotinoids and to replace WHO Class I products from older chemical classes. These innovative developments for life-cycle management, jointly with the introduction of generic products, will, within the next few years, turn neonicotinoids into the most important chemical class in crop protection.     

Comparative analysis of neonicotinoid binding to insect membranes: I. A structure-activity study of the mode of [3H]imidacloprid displacement in Myzus persicae and Aphis craccivora

Neonicotinoids bind selectively to insect nicotinic acetylcholine receptors with nanomolar affinity to act as potent insecticides. While the members of the neonicotinoid class have many structural features in common, it is not known whether they also share the same mode of binding to the target receptor. Previous competition studies with [3H]imidacloprid, the first commercialised neonicotinoid, indicated that thiamethoxam, representing a novel structural sub-class, may bind in a different way from that of other neonicotinoids. In the present work we analysed the mode of [3H]imidacloprid displacement by established neonicotinoids and newly synthesized analogues in the aphids Myzus persicae Sulzer and Aphis craccivora Koch. We found two classes of neonicotinoids with distinct modes of interference with [3H]imidacloprid, described as direct competitive inhibition and non-competitive inhibition, respectively. Competitive neonicotinoids were acetamiprid, nitenpyram, thiacloprid, clothianidin and nithiazine, whereas thiamethoxam and the N-methyl analogues of imidacloprid and clothianidin showed non-competitive inhibition. The chloropyridine or chlorothiazole heterocycles, the polar pharmacophore parts, such as nitroimino, cyanoimino and nitromethylene, and the cyclic or acyclic structure of the pharmacophore were not relevant for the mode of inhibition. Consensus structural features of the neonicotinoids were defined for the two mechanisms of interaction with [3H]imidacloprid binding. Furthermore, two sub-classes of non-competitive inhibitors can be discriminated on the basis of their Hill coefficients for imidacloprid displacement. We conclude from the present data that the direct competitors share the binding site with imidacloprid, whereas non-competitive compounds, like thiamethoxam, bind to a different site or in a different mode.     

Correlated responses to neonicotinoid insecticides in clones of the peach-potato aphid, Myzus persicae (Hemiptera: Aphididae)

BACKGROUND: Although there are still no confirmed reports of strong resistance to neonicotinoid insecticides in aphids, the peach-potato aphid (Myzus persicae Sulzer) shows variation in response, with some clones exhibiting up to tenfold resistance to imidacloprid. Five clones varying in response to imidacloprid were tested with four other neonicotinoid molecules to investigate the extent of cross-resistance.RESULTS: All four compounds-thiamethoxam, thiacloprid, clothianidin and dinotefuran-were cross-resisted, with ED(50) values ranked in the same order as for imidacloprid. Resistance factors ranged up to 11 for imidacloprid, 18 for thiamethoxam, 13 for thiacloprid, 100 for clothianidin and 6 for dinotefuran.CONCLUSION: This variation in response does not appear to be sufficient to compromise the field performance of neonicotinoids aimed at controlling aphids. However, it highlights the need for careful vigilance and stewardship in all M. persicae populations, and a need to consider neonicotinoids as a single cross-resisted group for management purposes.     

Effects of mutations in Drosophila nicotinic acetylcholine receptor subunits on sensitivity to insecticides targeting nicotinic acetylcholine receptors

Several strains of Drosophila melanogaster possess mutant alleles in nicotinic acetylcholine receptor (nAChR) subunits, Dα1 and Dβ2 that confer resistance to neonicotinoids such as imidacloprid and nitenpyram, and Dα6, that confers resistance to spinosyns. These mutant strains were bioassayed with a selected set of nAChR active insecticides including neonicotinoids, spinosad, and sulfoxaflor, a new sulfoximine insecticide. All of the neonicotinoids examined, except dinotefuran showed reduced insecticidal efficacy on larvae of the Dα1 mutant, suggesting that this subunit may be important in the action of these insecticides. All of the neonicotinoids, including dinotefuran, showed reduced insecticidal efficacy on larvae possessing the Dβ2 mutation. A similar pattern of broad neonicotinoid resistance to that of Dβ2 alone was also observed for larvae with both the mutations (Dα1 + Dβ2). The Dβ2 mutation exhibited a lower level of cross-resistance to sulfoxaflor (<3-fold) than to any of the neonicotinoids (>13-fold). In contrast, there was no cross-resistance for any of the neonicotinoids or sulfoxaflor in adult flies with the Dα6 mutation, which confers high levels of resistance to spinosad. Thus in the D. melanogaster strains studied, target site resistance observed for the neonicotinoids and the spinosyns does not translate directly to resistance towards sulfoxaflor.     

Quantitative correlation between molecular similarity and receptor-binding activity of neonicotinoid insecticides

Quantitative correlation between molecular similarity and receptor-binding activity of neonicotinoid insecticides such as imidacloprid and acetamiprid was studied by using a method of similarity index and semi-empirical molecular orbital calculations. A series of compounds having an aromatic ring and a cyclic or acyclic amine moiety with an electron-withdrawing group were subjected to the similarity-activity analysis. Energy-minimum structures and electrostatic properties of the molecules were obtained by MNDO-PM3. The electrostatic similarity of each molecule compared with the most active compounds was found to correlate significantly with the binding activity to nicotinic acetylcholine receptor (nAChR) in honey bee when the two molecules were superimposed to maximize the molecular shape similarity by simplex procedure. This indicates that molecular similarity in terms of electrostatic properties is important for activity, as well as superimposability in terms of molecular shape. A schematic model of interaction between neonicotinoids and nAChR is proposed according to the results of similarity-activity analyses. © 1998 SCI.     

新烟碱类杀虫剂亚致死剂量对麦长管蚜和棉蚜取食行为的影响

为了明确新烟碱类杀虫剂亚致死剂量对麦长管蚜和棉蚜拒食作用的差异,通过铷标记法、蜜露法以及两种蚜虫体内总糖、总脂含量的测定研究了新烟碱类杀虫剂亚致死剂量对麦长管蚜和棉蚜取食的影响。结果表明,铷标记法和蜜露法测定的新烟碱类杀虫剂亚致死剂量对麦长管蚜的拒食率均在80%以上,而对棉蚜的拒食率均在25%以下。蚜虫体内总糖总脂含量测定结果表明,新烟碱类杀虫剂亚致死剂量处理后麦长管蚜体内总糖、总脂含量均显著低于对照,而棉蚜体内总糖、总脂含量与对照均无显著差异。三种方法测定结果一致表明新烟碱类杀虫剂亚致死剂量对麦长管蚜具有很强的拒食作用,而对棉蚜没有明显的拒食作用。     

Incidence and characterisation of resistance to neonicotinoid insecticides and pymetrozine in the greenhouse whitefly,Trialeurodes vaporariorum Westwood (Hemiptera: Aleyrodidae)

BACKGROUND: Trialeurodes vaporariorum (Westwood), also known as the greenhouse whitefly, is a serious pest of protected vegetable and ornamental crops in most temperate regions of the world. Neonicotinoid insecticides are used widely to control this species, although resistance has been reported and may be becoming widespread. RESULTS: Mortality rates of UK and European strains of T. vaporariorum to a range of neonicotinoids and pymetrozine, a compound with a different mode of action, were calculated, and significant resistance was found in some of those strains. A strong association was found between neonicotinoids and pymetrozine, and reciprocal selection experiments confirmed this finding. Expression of resistance to the neonicotinoid imidacloprid and pymetrozine was age specific, and resistance in nymphs did not compromise recommended application rates. CONCLUSION: This study indicates strong parallels in the phenotypic characteristics of neonicotinoid resistance in T. vaporariorum and the tobacco whitefly Bemisia tabaci Gennadius, suggesting possible parallels in the underlying mechanisms. Copyright © 2010 Society of Chemical Industry