鱼尼汀受体作用剂类杀虫剂及其结构特点和机制

鱼尼汀受体作用剂类杀虫剂是一类高效、安全、作用机制独特的新颖杀虫剂。对此类杀虫剂的品种、结构特点及作用机制进行了概述。     

氟虫双酰胺的清洁合成法

氟虫双酰胺(flubendiamide)是具有独特作用机理的新杀虫剂,其作用靶标为鱼尼汀受体.简述了氟虫双酰胺以前的2种合成方法并指明了它们的弊端,详细介绍了氟虫双酰胺的清洁合成工艺.     

5%氟氯虫双酰胺悬浮剂的配方研制

制备了5%氟氯虫双酰胺悬浮剂。将原药、润湿分散剂、防冻剂、增稠剂均匀剪切后与氧化锆珠一起湿法砂磨,并对助剂进行单因素筛选优化配方。最终得到5%氟氯虫双酰胺悬浮剂的优选配方为：氟氯虫双酰胺5%、FS-30004%、20TX 2%、1601 2%、黄原胶0.2%、硅酸镁铝0.5%、乙二醇4%、1501 1%、去离子水补足至100%。制备的5%氟氯虫双酰胺悬浮剂热贮和冷贮后无分层、结底等现象。冷、热贮稳定性、悬浮率、持久起泡性等性能指标测试均合格,产品其他指标符合悬浮剂的要求。     

氟啶虫酰胺类衍生物的合成与生物活性测试

[目的]合成氟啶虫酰胺类衍生物,探究合成方法,并测试杀虫、杀菌活性.[方法]以中间体2,6-二氯-3-氰基-4-三氟甲基吡啶为起始原料,经3步反应合成氟啶虫酰胺类衍生物.并对其进行了红外,元素分析,1H NMR,MS结构表征和杀虫活性测试.[结果]以2,6-二氯-3-氰基-4-三氟甲基吡啶计总收率大于66％,合成的氟啶...     

20%氟虫双酰胺WG防治稻纵卷叶螟试验

试验结果表明,20%氟虫双酰胺WG150g/hm2防治稻纵卷叶螟,药后10d平均保叶效果达96.86%,防治效果达96.54%,与20%氯虫苯甲酰胺SC150mL/hm2处理相近,显著高于常规对照药剂阿维菌素、丙溴磷、毒死蜱的保叶和防治效果,稻谷增产率达8.94%。     

鱼尼汀受体及以其为靶标的杀虫剂的作用机理

介绍了鱼尼汀受体以其为靶标的杀虫剂的作用机理。     

氯虫苯甲酰胺、氟虫双酰胺对甜菜夜蛾酶活性的影响

[目的]研究氯虫苯甲酰胺、氟虫双酰胺半致死剂量处理后,甜菜夜蛾4龄幼虫的羧酸酯酶(CarE)、谷胱甘肽-S-转移酶(GST)活性的变化规律。[结果]CarE、GST活性测定结果显示,经过氯虫苯甲酰胺处理后CarE比活力在1 h达到最高,为147.83μmol/L/mg pro/30min,随后逐渐下降,处理后48 h比活力最低,但与0 h处理差异不显著;药剂处理后2 h,GST比活力为1.27 OD/mg pro/min,显著高于0、0.5、4、8、16、24、48 h处理的比活力。氟虫双酰胺处理后CarE、GST比活力均在1 h达到最大值,分别为15.18μmol/L/mg pro/30min、4.08 OD/mg pro/min,随着处理时间的增长,比活力均呈下降趋势,处理24 h后达到最低,但均与0 h处理差异不显著。[结论]氯虫苯甲酰胺、氟虫双酰胺处理甜菜夜蛾后可诱导CarE、GST活性增强,加快药剂的代谢,但随着处理时间的增加,其活性逐渐降低。     

氟虫双酰胺在土壤和白菜中的高效液相色谱分析

采用高效液相色谱法分析了土壤和白菜中的氟虫双酰胺,依次用乙腈和正己烷提取土壤和白菜中的氟虫双酰胺,提取液过弗罗里硅土柱净化,以甲醇-水(体积比1:3)作为流动相,使用C18反相色谱柱和紫外可变波长检测器,用外标法进行分析和定量.土壤中氟虫双酰胺的添加回收率为91.31%～94.80%,变异系数为2.57%～8.33%;白菜中氟虫双酰胺的添加回收率为89.19%～103.15%,变异系数为4.21%～5.43%;氟虫双酰胺在土壤和白菜中的最小检出量均为l×10-10g,最低检出质量分数均为0.003 mg/kg.     

氟啶虫酰胺衍生物的设计合成与生物活性

以石原产业的商品化杀虫剂氟啶虫酰胺为先导,通过变换吡啶环上羧基的位置,设计、合成了10种氟啶虫酰胺衍生物,并对其进行了~1H NMR结构表征和杀虫活性测试。杀虫活性测定结果初步表明,所设计、合成的部分氟啶虫酰胺衍生物在500 mg/L浓度下对苜蓿蚜有一定的杀虫活性,如化合物A2和A9对苜蓿蚜的致死率为30%。为氟啶虫酰胺类衍生物的设计合成提供参考。     

鱼尼丁受体杀虫剂Flubendiamine

本文介绍了鱼尼丁受体杀虫剂Flubendiamine的创制经纬、作用机制、生物活性、毒性及合成。     

4种鱼尼丁受体类杀虫剂活性研究

采用叶片饲喂法,在处理后72 h,测定了4种鱼尼丁受体类杀虫剂对3种鳞翅目害虫(黏虫、甜菜夜蛾、小菜蛾)的活性,为其合理使用提供依据。试验结果表明:四氯虫酰胺和氯虫苯甲酰胺对3种鳞翅目幼虫的活性较高,均高于氟苯虫酰胺和溴氰虫酰胺的活性;4种鱼尼丁受体类杀虫剂对小菜蛾卵基本无活性;在不同亚致死剂量下,4种鱼尼丁受体类杀虫剂处理小菜蛾后,可使小菜蛾幼虫的体重降低,发育速度变缓。应用该类杀虫剂防治鳞翅目害虫的最佳时期应为卵孵化盛期至低龄幼虫活动期。不同亚致死剂量的4种鱼尼丁受体类杀虫剂处理小菜蛾后,均能对小菜蛾幼虫的正常生长产生影响。     

鱼尼丁受体抑制剂及其作用机制研究进展

近年来,以鱼尼丁受体(ryanodine receptor,Ry R)为靶标的杀虫剂研发取得了突破性进展。介绍了Ry R结构和功能,以及Ry R为靶标的杀虫剂的创制历程,作用机制的研究进展。该类杀虫剂靶标新颖,作用机理独特、高效,对非靶标生物安全(如哺乳动物等)以及与传统农药无交互抗性,具有很好的发展前景。     

Molecular Characterization,mRNA Expression and Alternative Splicing of Ryanodine Receptor Gene in the Brown Citrus Aphid,Toxoptera citricida (Kirkaldy)

Ryanodine receptors (RyRs) play a critical role in regulating the release of intracellular calcium, which enables them to be effectively targeted by the two novel classes of insecticides, phthalic acid diamides and anthranilic diamides. However, less information is available about this target site in insects, although the sequence and structure information of target molecules are essential for designing new control agents of high selectivity and efficiency, as well as low non-target toxicity. Here, we provided sufficient information about the coding sequence and molecular structures of RyR in T. citricida (TciRyR), an economically important pest. The full-length TciRyR cDNA was characterized with an open reading frame of 15,306 nucleotides, encoding 5101 amino acid residues. TciRyR was predicted to embrace all the hallmarks of ryanodine receptor, typically as the conserved C-terminal domain with consensus calcium-biding EF-hands (calcium-binding motif) and six transmembrane domains, as well as a large N-terminal domain. qPCR analysis revealed that the highest mRNA expression levels of TciRyR were observed in the adults, especially in the heads. Alternative splicing in TciRyR was evidenced by an alternatively spliced exon, resulting from intron retention, which was different from the case of RyR in Myzus persicae characterized with no alternative splicing events. Diagnostic PCR analysis indicated that the splicing of this exon was not only regulated in a body-specific manner but also in a stage-dependent manner. Taken together, these results provide useful information for new insecticide design and further insights into the molecular basis of insecticide action.     

HIV-Tat Exacerbates the Actions of Atazanavir,Efavirenz, and Ritonavir on Cardiac Ryanodine Receptor (RyR2)

The incidence of sudden cardiac death (SCD) in people living with HIV infection (PLWH), especially those with inadequate viral suppression, is high and the reasons for this remain incompletely characterized. The timely opening and closing of type 2 ryanodine receptor (RyR2) is critical for ensuring rhythmic cardiac contraction–relaxation cycles, and the disruption of these processes can elicit Ca²⁺ waves, ventricular arrhythmias, and SCD. Herein, we show that the HIV protein Tat (HIV-Tat: 0–52 ng/mL) and therapeutic levels of the antiretroviral drugs atazanavir (ATV: 0–25,344 ng/mL), efavirenz (EFV: 0–11,376 ng/mL), and ritonavir (RTV: 0–25,956 ng/mL) bind to and modulate the opening and closing of RyR2. Abacavir (0–14,315 ng/mL), bictegravir (0–22,469 ng/mL), Rilpivirine (0–14,360 ng/mL), and tenofovir disoproxil fumarate (0–18,321 ng/mL) did not alter [³H]ryanodine binding to RyR2. Pretreating RyR2 with low HIV-Tat (14 ng/mL) potentiated the abilities of ATV and RTV to bind to open RyR2 and enhanced their ability to bind to EFV to close RyR2. In silico molecular docking using a Schrodinger Prime protein–protein docking algorithm identified three thermodynamically favored interacting sites for HIV-Tat on RyR2. The most favored site resides between amino acids (AA) 1702–1963; the second favored site resides between AA 467–1465, and the third site resides between AA 201–1816. Collectively, these new data show that HIV-Tat, ATV, EFV, and RTV can bind to and modulate the activity of RyR2 and that HIV-Tat can exacerbate the actions of ATV, EFV, and RTV on RyR2. Whether the modulation of RyR2 by these agents increases the risk of arrhythmias and SCD remains to be explored.     

Development of Urea and Thiourea Kynurenamine Derivatives: Synthesis,Molecular Modeling,and Biological Evaluation as Nitric Oxide Synthase Inhibitors

Herein we describe the synthesis of a new family of kynurenamine derivatives with a urea or thiourea moiety, together with their in vitro biological evaluation as inhibitors of both neuronal and inducible nitric oxide synthases (nNOS and iNOS, respectively), enzymes responsible for the biogenesis of NO. These compounds were synthesized from a 5‐substituted‐2‐nitrophenyl vinyl ketone scaffold in a five‐step procedure with moderate to high chemical yields. In general, the assayed compounds show greater inhibition of iNOS than of nNOS, with 1‐[3‐(2‐amino‐5‐chlorophenyl)‐3‐oxopropyl]‐3‐ethylurea (compound 5 n ) being the most potent iNOS inhibitor in the series and the most iNOS/nNOS‐selective compound. In this regard, we performed molecular modeling studies to propose a binding mode for this family of compounds to both enzymes and, thereby, to elucidate the differential molecular features that could explain the observed selectivity between iNOS and nNOS.     

A Combination of 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation Studies of Benzimidazole-Quinolinone Derivatives as iNOS Inhibitors

Inducible Nitric Oxide Synthase (iNOS) has been involved in a variety of diseases, and thus it is interesting to discover and optimize new iNOS inhibitors. In previous studies, a series of benzimidazole-quinolinone derivatives with high inhibitory activity against human iNOS were discovered. In this work, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular docking and molecular dynamics (MD) simulation approaches were applied to investigate the functionalities of active molecular interaction between these active ligands and iNOS. A QSAR model with R² of 0.9356, Q² of 0.8373 and Pearson-R value of 0.9406 was constructed, which presents a good predictive ability in both internal and external validation. Furthermore, a combined analysis incorporating the obtained model and the MD results indicates: (1) compounds with the proper-size hydrophobic substituents at position 3 in ring-C (R₃ substituent), hydrophilic substituents near the X₆ of ring-D and hydrophilic or H-bond acceptor groups at position 2 in ring-B show enhanced biological activities; (2) Met368, Trp366, Gly365, Tyr367, Phe363, Pro344, Gln257, Val346, Asn364, Met349, Thr370, Glu371 and Tyr485 are key amino acids in the active pocket, and activities of iNOS inhibitors are consistent with their capability to alter the position of these important residues, especially Glu371 and Thr370. The results provide a set of useful guidelines for the rational design of novel iNOS inhibitors.     

不同分子量磺酰化魔芋葡甘聚糖的制备与生物活性研究

利用纤维素酶降解原始魔芋葡甘聚糖,制得魔芋葡甘低聚糖,以N,N-二甲基甲酰胺为溶胀剂,用吡啶-氯磺酸法制备了一系列分子量不同而取代度相近的磺酰化魔芋葡甘聚糖(KGMS).通过对KGMS分子量的测试,探讨了磺酰化条件对磺酰化衍生物的影响;以红外光谱、元素分析等表征其结构,并通过生物活性测试(包括体外抗凝血时间、体外抗肿瘤活性、抑菌活性等),探讨了不同分子量的磺酰化魔芋葡甘聚糖的生物活性.