Affinity to the Nicotinic Acetylcholine Receptor and Insecticidal Activity of Chiral Imidacloprid Derivatives with a Methylated Imidazolidine Ring

Four imidacloprid derivatives with an asymmetrically methylated imidazolidine ring were synthesized. Their affinity to the nicotinic acetylcholine receptor of housefly Musca domestica and insecticidal activity against the housefly were measured. The compound with a 5R-methylated imidazolidine ring demonstrated intrinsic activity comparable to that of the unsubstituted compound. Most of the compounds were synergized by oxygenase inhibitors.     

Synthesis of imidacloprid derivatives with a chiral alkylated imidazolidine ring and evaluation of their insecticidal activity and affinity to the nicotinic acetylcholine receptor

A series of imidacloprid (IMI) derivatives with an alkylated imidazolidine ring were asymmetrically synthesized to evaluate their insecticidal activity against adult female housefly, Musca domestica, and affinity to the nicotinic acetylcholine receptor of the flies. The bulkier the alkyl group, the lower was the receptor affinity, but the derivatives methylated and ethylated at the R-5-position of the imidazolidine ring were equipotent to the unsubstituted compound. Quantitative structure–activity relationship (QSAR) analysis of the receptor affinity demonstrated that the introduction of a substituent into the imidazolidine ring was fundamentally disadvantageous, but the introduction of a substituent at the R-5-position was permissible in the case of its small size. The binding model of the synthesized derivatives with the receptor supported the QSAR analysis, indicating the existence of space for a short alkyl group around the R-5-position in the ligand-binding site. In addition, positive correlation was observed between the insecticidal activity and receptor affinity, suggesting that the receptor affinity was the primary factor in influencing the insecticidal activity even if the imidazolidine ring was modified.     

Synthesis and Insecticidal Activity of Isobutenyl- and Isobutyl-cyclopropanecarboxylates

Several isobutenyl- and isobutyl-cyclopropanecarboxylates were synthesized. The insecticidal activities against the housefly of their 5-benzyl-3-furylmethyl or allethronyl esters were tested. Among the substituents on the cyclopropane ring, a methyl group cis to the ester linkage has been found to be essential for toxicity against the housefly and a trans-isobutenyl group greatly enhances the toxic activity.     

Synthesis of phosphotriester by DCC and its biological activities

The synthesis of a phosphotriester, an inhibitor of acetylcholinesterase, was performed by the coupling reaction of diethylphosphate with various phenolic compounds using dicyclohexylcarbodiimide (DCC). All of the compounds synthesized inhibited housefly acetylcholinesterase activity. Derivatives including an electronegative part as a nitro group in the phenol ring showed strong inhibition towards housefly acetylcholinesterase, but those with hydrophobic derivatives of the phenol group, such as cresol, naphthol and biphenol, showed relatively low inhibition. In experiments with housefly, the value of LD50 for each chemical correlated with the I50 value for acetylcholinesterase except alpha-naphthyl diethylphosphate, beta-naphthyl diethylphosphate and p,p'-biphenyl diethylphosphate.     

Configurational Relationship between Substituents on Cyclopropane Ring of Pyrethroids and Their Insecticidal Toxicity

Several methyl-substituted cyclopropanecarboxylates were prepared and their steric configurations were established. The insecticidal activity against the housefly of their 5-benzyl-3-furylmethyl esters were tested. Among the substituents on cyclopropane ring, cis-methyl group to ester linkage has been found to be the most essential part for toxicity and trans-methyl and trans-isobutenyl groups greatly enhance its toxic activity.     

Alantrypinone and its derivatives: Synthesis and antagonist activity toward insect GABA receptors

The γ-aminobutyric acid (GABA) receptor bears important sites of action for insecticides. Alantrypinone is an insecticidal alkaloid that acts as a selective antagonist for housefly (vs rat) GABA receptors, and is considered to be a lead compound for the development of a safer insecticide. In an attempt to obtain compounds with greater activity, a series of racemic alantrypinone derivatives were systematically synthesized using hetero Diels–Alder reactions, and a total of 34 compounds were examined for their ability to inhibit the specific binding of [³H]4′-ethynyl-4-n-propylbicycloorthobenzoate, a high-affinity non-competitive antagonist, to housefly-head membranes. The assay results showed that (1) there is no significant difference between the potencies of natural (+)-alantrypinone and its synthetic racemate; (2) the amide NHs at the 2- and 18-positions are important for high activity; (3) there is a considerable drop in potency for compounds without an aromatic ring at the 16-position; and (4) a large substituent at the 3-position is detrimental to high activity.     

家蝇幼虫组织匀浆液的抗病毒活性

以家蝇Musca domesticaL.幼虫为材料,研究了蝇蛆组织匀浆液的抗病毒活性。用鸡胚培养检测了其抗流感病毒的活性,乙型肝炎病毒表面抗原诊断试剂盒检测了其对乙型肝炎病毒表面抗原的破坏作用。结果表明:15μL的家蝇幼虫组织匀浆液对流感病毒的抑制率为72.41%,而30,50和80μL剂量组对病毒的杀灭率都达到80%以上;蝇蛆组织匀浆液对乙型肝炎病毒表面抗原的破坏率可达到87.5%。说明家蝇幼虫体内存在着抗病毒活性物质。这为开发天然的抗病毒药物提供了新的途径。     

Synthesis of 2-(2′-Hydroxy-2′, 2′-diphenylethyl)-8-hydroxy-quinoline and Its Biological Activity

2-(2′-Hydroxy-2′,2′-diphenylethyl)-8-hydroxyquinoline was prepared via Grignard reaction involving the activated methyl group in position 2. This compound inhibited the action of the phenol oxidase prepared from prepupae of housefly. In a dipping test of the final instar larvae of housefly, it showed some inhibitory effects on the metamorphosis.     

Super agonist actions of clothianidin and related compounds on the SAD beta 2 nicotinic acetylcholine receptor expressed in Xenopus laevis oocytes

To compare the actions of clothianidin, a neonicotinoid acting on insect nicotinic acetylcholine receptors, and related compounds with that of imidacloprid, the compounds were tested on the Drosophila SAD-chicken beta2 nicotinic acetylcholine receptor expressed in Xenopus laevis oocytes using two-electrode voltage-clamp electrophysiology. The maximum response of the SAD beta 2 nicotinic receptor to clothianidin was larger than that observed for acetylcholine. Ring breakage of the imidazolidine ring of imidacloprid resulting in the generation of a guanidine group was critical for this super agonist action.     

Studies on the Syntheses of the Pyrethrin Analogues and their Biological Activities

Some new allethronyl esters of cyclopropanecarboxylic acids were prepared, and their insecticidal activities were tested against common housefly. Allethronyl esters of cyclopropanecarboxylic acids having 3,4-methylenedioxyphenyl group on the cyclopropane ring were more or less toxic. Among them, allethronyl 2,2-dimethyl-3-(3′,4′-methylenedioxyphenyl)-cycloopropane-l-carboxylate was found to be more toxic than α-dl-trans-allethrin, and the calculated relative effectiveness were 1.48 and 1.21 on the mortality and knock-down activity respectively as compared with α-dl-trans-allethrin.     

对虾暴发性流行病的群体感染及投饲蝇幼的抗病机制研究

通过对虾的室内人工感染和野外群体感染,建立了对虾暴发性流行病的群体感染模型,分析了投饲绳幼的抗病机制。结果表明,合理投饲蝇蛆的对虾,50％死亡时间较对照组延迟3－5倍;病毒感染对虾7－10d前投喂蝇幼,蝇幼激活了对虾酚氧化酶系统,酚氧化酶活力较对照组提高约3倍;对虾群体感染模型的建立,直观地说明了蝇幼在提高对虾抗杆状病毒感染过程中发挥的重要作用。     

溴氰菊酯对不同品系家蝇脑突触体膜蛋白磷酸化及ATP酶活性的影响

以敏感品系家蝇和溴氰菊酯抗性品系家蝇(Musca domestica L.)为材料,研究和比较了神经毒剂溴氰菊酯对其脑突触体蛋白磷酸化作用的影响。结果表明,浓度为10^-5 mol/L溴氰菊酯抑制了敏感品系家蝇脑突触体蛋白磷酸化作用,而对抗性品系家蝇脑突触体蛋白磷酸化作用无明显影响。若反应体系中加入2.5×10^-6 mol/L的cAMP显著激活了敏感品系家蝇脑突触体蛋白磷酸化水平,但是当0.6 mmol/Lca²⁺或0.6 mmol/L Ca²⁺加10^-5 mol/L钙调蛋白时明显增强了抗性品系家蝇脑突触体蛋白磷酸化水平,甚至超过了其对敏感品系的作用水平。此外,还发现不同浓度的溴氰菊酯可抑制突触膜上的Na/K-ATP酶和Ca-ATP酶活力,浓度越高抑制作用也越大,并且敏感品系家蝇对溴氰菊酯的敏感度要高于抗性品系。     

N-甲基取代苯基氨基甲酸酯的系列合成及其对家蝇的生物活性

利用酰氯水相简易工艺合成了52个N-甲基取代苯基氨基甲酸酯类化合物, 并测定了它们对家蝇Musca domestica的室内毒力。结果表明：烷基单取代化合物中,间位取代物的活性大于邻、对位;单卤素取代物中,邻位取代活性大于间位和对位,邻溴代物大于邻氯代物;对位硫甲基和邻位硫乙基取代物的活性均较高。对于烷基间位苯环取代化合物,在一定限度内随烷基分子量增大,化合物对家蝇的毒力增高,其次序为异丙基>乙基>甲基>未取代基。     

家蝇幼虫提取物对辐射小鼠的免疫调节作用

研究了家蝇Musca domestica幼虫提取物对辐射小鼠的免疫调节作用。测定了小鼠的脏器官指数,NK细胞活性,T、B淋巴细胞增值活性及小鼠血清SOD活性和MDA含量等指标。结果表明：经口给予一定剂量的家蝇幼虫提取物对辐射和未辐射小鼠的脾脏指数和胸腺指数变化有显著影响,均可提高NK细胞活性,T、B淋巴细胞增值活性及小鼠血清SOD活性,同时可降低小鼠血清中的MDA含量。结果显示家蝇幼虫提取物对辐射和未辐射小鼠均具有较好的免疫调节作用。     

显微注射法制备转基因家蝇技术的建立

旨在利用显微注射法对早期家蝇(Musca domestica L.)卵注射含有增强型绿色荧光蛋白(Enhanced green fluorescent protein,EGFP)基因的转座子载体,实现活体基因稳定表达并对其进行验证,为开展家蝇基因功能的研究奠定基础。文中自制适用于显微注射家蝇卵的硼硅酸盐玻璃微量注射针,摸索出家蝇卵壳的软化处理条件,以NanojectⅢ高精度微量注射器为主体构建适用于家蝇的显微注射技术平台;将含有眼部特异表达的3×P3启动子、EGFP的重组质粒PiggyBac-[3×P3]-EGFP与稳定遗传表达辅助质粒pHA3pig helper显微注射到处理过的家蝇卵中,待羽化观察眼部发光情况,检测EGFP的表达及转录水平。结果表明,将家蝇卵在漂白水中漂洗35 s时卵的正常孵化率为55%,处理35 s的卵壳其硬度适宜注射且注射针头不易破碎;羽化后的家蝇眼部带有绿色荧光的占比约为3%,通过分子检测,家蝇的DNA和RNA中均扩增出EGFP特异片段,大小为750 bp。通过该技术平台,能够便捷、有效地实现报告基因在家蝇中的稳定表达,建立以家蝇为主体的生物反应器,为后续家蝇基因功能的研究提供一定参考价值。     

Antimicrobial Activity of 3-Phenylimidazolidine-2,4-diones and Related Compounds

The structure-activity relationships of 3-(3′,5′-dichlorophenyl)imidazolidine-2,4-dione derivatives were investigated by the agar dilution method using Sclerotinia sclerotiorum as a test microbe. Several compounds were tested for antimicrobial spectrum in vitro with other pathogenic microbes and for foliage protective activity in green house tests with rice sheath blight, rice brown spot, damping-off of cucumber and kidney bean stem rot. It was found that the antimicrobial activity was enhanced when the 1-position of imidazolidine ring was substituted by an alkyl group but was reduced when the 5-position was substituted by alkyl groups. Generally, 3-(3′,5′-dichlorophenyl)imidazolidine-2,4-dione derivatives were active against Scierotiniaceae, Corticiaceae, Dematiaceae, Polystigmataceae or Pleosporaceae. In green house tests, some of these compounds showed high protective activity against rice sheath blight, rice brown spot, damping-off of cucumber and kidney bean stem rot. Results of the green house tests on the above mentioned diseases correlate well with those of in vitro tests except in the case of kidney bean stem rot.     

阿特拉津和敌敌畏对棉铃虫和家蝇羧酸酯酶以及GSH—S—转移酶的诱导作用

在一定时间内,刚特拉津 (Atrazinc)对棉铃虫 Heliothis armigera 幼虫羧酸酯酶以及GSH-S-转移酶(GST)活性有明显的诱导作用,羧酸酯酶活性最高增加146%,GST增加280%。 对羧酸酯酶的诱导高峰时间要落后于GST,不同施药剂量的诱导高峰时间以及导增加的量也不相同。 敌敌畏对家蝇Musca domestica vicina GST活性没有明显的诱导作用,阿特拉津对家蝇GST活性也没有产生诱导作用。     

A C-terminal aldehyde analog of the insect kinins inhibits diuresis in the housefly

The insect kinins are present in a wide variety of insects and function as potent diuretic peptides in flies. A C-terminal aldehyde insect kinin analog, Fmoc-RFFPWG-H (R-LK-CHO), demonstrates stimulation of Malpighian tubule fluid secretion in crickets, but shows inhibition of both in vitro and in vivo diuresis in the housefly. R-LK-CHO reduced the total amount of urine voided over 3 h from flies injected with 1 microL of distilled water by almost 50%. The analog not only inhibits stimulation of housefly fluid secretion by the native kinin Musdo-K, but also by thapsigargin, a SERCA inhibitor, and by ionomycin, a calcium ionophore. The activity of R-LK-CHO is selective, however, as related C-terminal aldehyde analogs do not demonstrate an inhibitory response on housefly fluid secretion. The selective inhibitory activity of R-LK-CHO on housefly tubules represents an important lead in the development of environmentally friendly insect management agents based on the insect kinins.     

DIFFERENCES IN SUSCEPTIBILITY TO INSECTICIDES BETWEEN ADULTS AND LARVAE OF HOUSEFLY, MUSCA DOMESTICA (L.)

Abstract  In this paper, we reported the differences in susceptibility to insecticides between adults and larvae of housefly, Musca domestica (L.), and the mechanisms for the differences. The larvae of housefly were much more tolerant to insecticides than the adults, and the tolerance ratio to cyhalothrin was as high as 205.5 for susceptible strain. Mechanism studies showed that higher GST activity was associated with higher insecticide tolerance in the larvae. The co-toxicity coefficient of the mixture of cyhalothrin and methylene dithiocyanate(4:1) on pyrehid-resistant houseflies was 188.     

Antimicrobial activity of some 2-amino-5-subsituted pyridine derivatives

A series of 2-amino-5-substituted pyridine derivatives were prepared and evaluated against phytopathogenic fungi and bacteria under laboratory conditions. Position 4 on the pyridine ring has notable fungicidal and bactericidal activity, greater than position 3 and/or position 6. Reaction of 1-hydroxymethyl benzotriazole with the amino group of the pyridine ring gave better fungicidal activity than substitution on the carbon of the pyridine ring (compound 4 versus 1c). Replacing the benzotriazole moiety with thiophenol exhibited the strongest fungicidal and bactericidal activity in this series (compound 3).