A new pyrethroid of high insecticidal activity

New pyrethroids containing heterocyclic rings in the alcohol moieties were synthesised and their insecticidal activities were studied. Of these new pyrethroids, 3-benzylpyrrol-1-ylmethyl (1RS-cis, trans-3(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate was found to be the most effective, having higher activity than permethrin against Musca domestica by a topical application method. In addition, para-substituted analogues of the 3-benzylpyrrol-1-ylmethyl ester were also synthesised to study the substituent effects on insecticidal activities; the residual effects of these compounds against Blattella germanica were also examined.     

Action of pesticides on earthworms. Part III: Inhibition and reactivation of cholinesterases in Eisenia foetida (Savigny) after treatment with cholinesterase-inhibiting insecticides

The degree of inhibition and the rate of recovery of total cholinesterase level were investigated after in-vivo treatment of the earthworm Eisenia foetida (Savigny) with aldicarb, carbaryl, carbofuran, oxamyl, and the O-analogues of bromophos (bromo-phosoxon), parathion (paraoxon), parathion-methyl (paraoxon-methyl), and trichloronate (trichloronatoxon). The results can be explained by the presence of two cholinesterases (E1 and E2), which were demonstrated by in-vitro inhibition studies. E1 was the most sensitive to all the inhibitors tested. The in-vivo reactivation rate after inhibition with paraoxon was very high for E1 and very low for E2. Therefore, pretreatment with paraoxon probably increased the toxicity of carbaryl. It was concluded that the toxicity towards E. foetida can be explained in terms of cholinesterase inhibition, provided that the action on the two cholinesterases and the worms' tolerance for a transient but almost total cholinesterase depression are taken into account. Data are given showing that two other species of earthworms also contain different types of cholinesterases with respect to reactions with inhibitors.     

The toxicity of benomyl and some related 2-substituted benzimidazoles to the earthworm Lumbricus terrestris

Benzimidazole and its 2-amino analogue were non-toxic to Lumbricus terrestris when administered orally. The fungicidal 2-substituted benzimidazoles (benomyl, carben-dazim, fuberidazole and thiabendazole) and l-(benzimidazol-2-yl)-3-butylurea were highly and equally toxic. The equitoxicity of compounds with widely differing substituent groups suggests a common mode of action—the benzimidazole moiety being the active part of the molecule. It is likely that there is a common mode of action for benzimidazole analogues for both fungicidal activity and earthworm toxicity. There was no detectable effect on the cholinesterase levels of earthworms poisoned by benomyl. But it is confirmed that the cholinesterase inhibitory activity of benomyl in vitro is due to formation of butyl isocyanate.     

Fumigant and contact toxicity of Myrtaceae plant essential oils and blends of their constituents against adults of German cockroach (Blattella germanica) and their acetylcholinesterase inhibitory activity

Fumigant and contact toxicities of 11 Myrtaceae plant essential oils and their constituents against adult male and female Blattella germanica were evaluated. Of 11 Myrtaceae plant essential oils, Eucalyptus polybractea, Eucalyptussmithii, Eucalyptusradiata, Eucalyptusdives, Eucalyptusglobulus, and Melaleuca uncinata, showed 100% fumigant toxicity against adult male German cockroaches at a concentration of 7.5 mg/liter air concentration. In contact toxicity tests, E. polybractea, E. smithii, E. radiata, E. dives, E. globulus, Melaleucadissitiflora, and M. uncinata produced strong insecticidal activity against adult male and female German cockroaches. Of the essential oil constituents, terpinolene, α-terpinene, and terpinen-4-ol demonstrated strong fumigant toxicity against adult male and female B. germanica. Eugenol, isoeugenol, methyl eugenol, and terpinen-4-ol showed strong contact toxicity against adult male B. germanica. The toxicity of the constituent blends identified from M. dissitiflora essential oils indicated that terpinen-4-ol were major contributor to the fumigant activity or contact toxicity of the artificial blend. Only isoeugenol exhibited inhibition activity against male acetylcholinesterase. IC₅₀ values of isoeugenol were 0.22 mg/mL against male acetylcholinesterase.     

Binding activity of substituted benzyl derivatives of chloronicotinyl insecticides to housefly‐head membranes,and its relationship to insecticidal activity against the housefly Musca domestica

Variously substituted benzyl derivatives of chloronicotinyl insecticides were synthesized with a wide range of substituents including halogens, NO₂, CN, CF₃ and small alkyl and alkoxy groups at the ortho, meta and para positions, as well as multiple‐substituted benzyl analogues. Their binding activity to the α‐bungarotoxin binding site in housefly (Musca domestica) head membrane preparations was measured. Among the compounds tested, the activity of the meta‐CN derivative was the highest, being 20–100 times higher than those of imidacloprid, acetamiprid and nitenpyram. The synergized insecticidal activity against houseflies was also measured for selected compounds with the metabolic inhibitor, NIA16388 (propargyl propyl phenylphosphonate). For the nitromethylene analogues, including both benzyl and pyridylmethyl analogues, higher binding activity usually resulted in higher insecticidal activity. © 2000 Society of Chemical Industry     

Fipronil metabolism,oxidative sulfone formation and toxicity among organophosphate‐ and carbamate‐resistant and susceptible western corn rootworm populations

Fipronil toxicity and metabolism were studied in two insecticide‐resistant, and one susceptible western corn rootworm (Diabrotica virgifera virgifera, LeConte) populations. Toxicity was evaluated by exposure to surface residues and by topical application. Surface residue bioassays indicated no differences in fipronil susceptibility among the three populations. Topical bioassays were used to study the relative toxicity of fipronil, fipronil + the mono‐oxygenase inhibitor piperonyl butoxide, and fipronil's oxidative sulfone metabolite in two populations (one resistant with elevated mono‐oxygenase activity). Fipronil and fipronil‐sulfone exhibited similar toxicity and application of piperonyl butoxide prior to fipronil resulted in marginal effects on toxicity. Metabolism of [¹⁴C]fipronil was evaluated in vivo and in vitro in the three rootworm populations. In vivo studies indicated the dominant pathway in all populations to be formation of the oxidative sulfone metabolite. Much lower quantities of polar metabolites were also identified. In vitro studies were performed using sub‐cellular protein fractions (microsomal and cytosolic), and glutathione‐agarose purified glutathione‐S‐transferase. Oxidative sulfone formation occurred almost exclusively in in vitro microsomal reactions and was increased in the resistant populations. Highly polar metabolites were formed exclusively in in vitro cytosolic reactions. In vitro reactions performed with purified, cytosolic glutathione‐S‐transferase (MW = 27 kDa) did not result in sulfone formation, although three additional polar metabolites not initially detectable in crude cytosolic reactions were detected. Metabolism results indicate both cytochromes P450 and glutathione‐S‐transferases are important to fipronil metabolism in the western corn rootworm and that toxic sulfone formation by P450 does not affect net toxicity. © 2000 Society of Chemical Industry     

Synthesis and insecticidal properties of ether analogues of DDT-pyrethroids

Twenty-seven ethers which are structural analogues of DDT-pyrethroid insecticides have been synthesised. Bioassay data for these compounds against Lucilia cuprina, Blatella germanica and Heliothis punctigera are presented and the structure-activity relationships (SAR) discussed. The SAR of the new series of ether analogues are compared and contrasted to those of their parent DDT-pyrethroid compounds.     

Comparative toxicology of AC 217,300 in various species of insects

AC 217,300 was highly toxic by topical application to adult Musca domestica and Blattella germanica, and larvae of Spodoptera eridania, with LD₅₀ values in μg/g of 20, 19, and 61, respectively. It was relatively nontoxic to Diabrotica undecimpunctata howardi beetles and Heliothis virescens larvae with LD₅₀ values of 165 and >883. When incorporated into baits, AC 217,300 was still highly toxic to M. domestica, B. germanica, and S. eridania. A significant increase in toxicity to H. virescens was observed although the percentage mortality was only 45%. AC 217,300 was not effective against D. undecimpunctata with either mode of application. A comparison of toxicity with tissue residues indicated that AC 217,300 was highly toxic to M. domestica, B. germanica, H. virescens, and S. eridania if it was absorbed. However, D. undecimpunctata appeared to be much less sensitive to AC 217,300, as only 18% mortality was observed with corresponding tissue concentrations two to six times those producing 95–100% mortality in M. domestica and S. eridania. Exposure of M. domestica to an AC 217,300-treated bait for 3–6 hr was sufficient to cause 50–100% mortality after 2 days and 95–100% mortality by 7 days. With B. germanica, a 1- to 3-day exposure resulted in 75–90% control within 7 days, while exposure for 3–7 days gave 90–100% control. Environmental temperature had a pronounced effect on the toxicity of AC 217,300 to both M. domestica and B. germanica. A 20-fold increase in toxicity was observed when the environmental temperature was raised from 21 to 32°C. This observation, in concert with the symptoms of intoxication, support the hypothesis that AC 217,300 is an inhibitor of energy production. Approximately 85 and 87% of the total residue of AC 217,300 extracted from treated M. domestica and B. germanica, respectively, was parent material. Six minor metabolites were detectable, of which three were tentatively identified by cochromatography with authentic standards. None of the identified metabolites had any insecticidal activity in vivo, suggesting that AC 217,300 is the actual toxicant.     

O-ethyl O-isopropyl O-(5-methoxy-1-methyl-6-oxo-1H-pyridazin-4-yl) phosphorothioate,a new experimental insecticide and acaricide

The insecticidal and acaricidal action, anti-cholinesterase activity and toxicity to rats of a new experimental pesticide, O-ethyl O-isopropyl O-(5-methoxy-1-methyl-6-oxo-1H-pyridazin-4-yl) phosphorothioate ( I ), and those of some by-products found in the technical material, are described. High insecticidal and acaricidal effectiveness of I was found in laboratory and field trials. The activity as a soil insecticide in field trials was equal to, or greater than, that of other chemicals used at present.     

Block of electron transport by surangin B in bovine heart mitochondria

Exposure of mitochondria isolated from bovine heart to the insecticidal coumarin surangin B results in inhibition of complex II (IC₅₀ = 0.2 μM), III (IC₅₀ = 14.8 μM), and IV (IC₅₀ = 3.1 μM), but in contrast, the NADH:ubiquinone reductase (complex I) was completely insensitive to this compound at 100 μM. Kinetic analysis of surangin B’s interaction with complex II was then investigated using sub-mitochondrial particles. With succinate as the substrate, surangin B, like carboxin, acted with non-competitive kinetics and clearly contrasted in its action with malonate, a competitive inhibitor of complex II. Likewise, surangin B acted as a non-competitive inhibitor of decylubiquinone-dependent interception of electrons at complex II. Difference spectra of reduced complex III equilibrated with surangin B were found to closely parallel those of antimycin A, but were different in nature to those of the Q_o site inhibitors myxothiazol and famoxadone. Investigation of surangin B-dependent functional perturbation of complex III used the synthetic electron acceptor 2-nitrosofluorene, which intercepts electrons specifically from the Q_i site. These experiments demonstrated that like antimycin A, surangin B acts as a selective blocker of electron diversion to 2-nitrosofluorene through Q_i within complex III. We conclude that surangin B blocks electron transport at several points in bovine heart mitochondria, however, complex I is spared. The potent inhibitory action of surangin B on complex II involves binding to a site which is distinct from both the succinate binding site and the domain responsible for interacting with ubiquinone. Surangin B apparently blocks complex III by interacting with the Q_i (antimycin A-binding) pocket.     

The activity of some pyrethroids against Periplaneta americana and Blattella germanica

The knockdown and contact killing actions of various pyrethroids were compared using Blattella germanica and Periplaneta americana. A wide range of knockdown activity was found; 5-benzyl-3-furylmethyl (1R)-cis-3-(dihydro-2-oxo-3-thienylidenemethyl)-2,2-dimethylcyclopropanecarboxylate (RU 15525) acted fastest, more rapidly than pyrethrins, against B. germanica as well as having a low LD₅₀ value. Topical application and direct spray tests showed that (S)-α-cyano-3-phenoxybenzyl (1R)-cir-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (NRDC 161) was more active as a killing agent, by an order of magnitude, than cismethrin, the next most active compound, and also had considerable knockdown activity. Piperonyl butoxide generally had little synergist effect. Female P. americana were over three times more tolerant than males to a range of insecticides applied topically. Residual knockdown action in the WHO resistance test was observed to provide baseline data. There was little overlap in speed of action between pyrethroids and other insecticides among the compounds tested.     

Permethrin as a residual insecticide against cockroaches

The pyrethroid permethrin was shown to be active against Blattella germanica, Periplaneta americana and Blatta orientalis. In laboratory tests on plywood panels the best formulation was a 25% wettable powder which showed an initial LC₅₀ of 10 mg m^?2 against B. germanica and lost activity at the weekly rate of 1.9 mg m^?2. An initial deposit of 108 mg m^?2 gave 50% kill after one year. The synergist piperonyl butoxide diminished residual performance. In one field trial, good control was maintained for more than four months with an initial deposit of 50 mg m^?2, the smallest dose used. From this and other trials, the recommended rate of application for general use in long-term control is 100 mg m^?2. A distinctive slow expellent action against B. germanica was seen in field trials.     

雷公藤根皮提取物对茭白二化螟的生物活性

研究了雷公藤根皮乙醇提取物对茭白二化螟的生物活性 ,结果表明 ,提取物对二化螟幼虫有较强的拒食作用、生长发育抑制作用、毒杀作用和内吸毒力。对 2龄 1日幼虫选择性与非选择性的拒食中浓度 (AFC₅₀)分别为111.57μg/mL和 144.28μg/mL ,生长发育的抑制中浓度 (EC₅₀)为 134.39μg/mL。内吸毒杀作用在 1600μg/mL浓度下能达到 90%以上 ,胃毒作用在 800μg/mL下 ,处理 5d后的死亡率为 73.71% ,对二化螟蚁螟的触杀作用不明显 ,对天敌螟黄足绒茧蜂安全。     

The optical isomers of α-cyano-3-phenoxybenzyl 3-(1,2-dibromo-2,2-dichloroethyl)-2,2-dimethylcyclo-propanecarboxylate and their insecticidal activities

Bromination of the dichlorovinyl group of cypermethrin yielded a new compound which is a highly potent insecticide. This dibromo adduct has four asymmetric centres and therefore can exist as a mixture of 16 stereoisomers. To establish the influence of the absolute configuration at the chiral centres on the biological activities of these isomers, each of the isomers was isolated; their insecticidal activities against larvae of Heliothis virescens, and adult Calliphora erythrocephala and Blattella germanica were then determined and compared with those of (S)-α-cyano-3-phenoxybenzyl (1R)-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (deltamethrin NRDC 161), of fenvalerate, and of the eight stereoisomers of cyper methrin.     

2-arylalkanoates,a new group of synthetic pyrethroid esters not containing cyclopropanecarboxylates

Although structure modifications of natural pyrethrin constituents have disclosed a variety of potent synthetic analogues, all known examples are cyclopropanecarboxylate esters, a grouping that appeared to be essential for insecticidal activity. Some new substituted 2-phenylalkanoates, whose biological activities are of a similar nature and potency to those of conventional pyrethroids, are now reported. 5-Benzyl-3-furylmethyl and 3-phenoxybenzyl 3-methyl-2-phenylbutyrates and their analogues are potent insecticides. Activity is increased on the introduction of appropriate groups into the 3 and/or 4-positions of the aryl ring and the (S)-2-phenylalkanoates are far more active than their (R)-enantiomorphs. Structure/activity relationships are compared with those for conventional pyrethroids. Some of the new series compare favourably with typical insecticides in tests against Musca domestica, Spodoptera litura and Plutella xylostella.     

Transformation of aldicarb sulfoxide and aldicarb sulfone in four water-saturated sandy subsoils

The transformation of aldicarb sulfoxide and aldicarb sulfone was studied in incubations with water-saturated subsoils under simulated field conditions at 10°C. The subsoils were collected at four locations from beneath the water table at a depth of 2.5 to 3.5 m. In three of the subsoils, the half-life of sulfoxide, incubated at concentrations of 0.14-0.17 mg litre^?1, ranged from 0.7 to 2.8 years. At higher concentrations (8-13 mg litre^?1), its half-life ranged from 3.4 to 6.4 years. At the lower concentration, a large fraction of sulfoxide was transformed into sulfone. The rates of transformation of the sulfone at the lower concentration in the three subsoils corresponded to half-lives of 3.3 to 8.1 years, but in only one subsoil was a significant transformation rate (half-life 6.7 years) measured at the higher concentration during the 2.3-year incubation period. The half-lives at the lower concentrations were more like those in field studies, and perhaps would still underestimate transformation rates under field conditions. After a year, 2.5-15% of the higher sulfoxide and sulfone doses had been trapped as [¹⁴C] carbon dioxide. In the fourth subsoil, with more anaerobic conditions, the half-life of sulfoxide at both concentrations was less than 0.02 year and that of sulfone was about 0.04 year. Four or five radio-labelled transformation products could be traced in this subsoil and about half of the dose of both compounds was trapped as [¹⁴C] carbon dioxide.     

The pyrethrins and related compounds; Part XXIV: synthesis, 13C-nuclear magnetic resonance spectra and insecticidal activity of cycloalkyl analogues of fenvalerate

Close isosteres of fenvalerate [(RS)-α-cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate], in which cyclopropyl groups replace isopropyl have insecticidal activity close to or greater than the parent compounds, and diminished intravenous toxicity to rats. A direct toxicological relationship of these compounds to fenvalerate itself and to chrysanthemate esters is indicated by the consistently greater activity of esters from one of an enantiomeric pair of acids. Other esters with larger alkyl or cycloalkyl groups, or spiropentane analogues of chrysanthemates are less active insecticides. ¹³C-Nuclear magnetic resonance spectra suggest that in the α-cyanobenzyl esters there is an intramolecular through-space interaction in solution. The relationships between the chemical structures of the compounds synthesised and their relative activities to different insect species and toxicity to rats are discussed.     

Comparative properties of N-acetyl derivatives of oxime N-methylcarbamates and aryl N-methylcarbamates as insecticides and acetylcholinesterase inhibitors

N-acylation of aryl N-methylcarbamates is known to reduce their mammalian toxicity considerably without adversely affecting their insecticidal activity. It has now been found that N-acylation of several insecticidal oxime carbamates results in loss of toxicity both to insects and mammals. Kinetic data for base-catalysed solvolysis and inhibition of acetylcholinesterase, together with published work on metabolism, are combined to provide a rationale for this unexpected observation and to account for the selective toxicity of aryl N-acetyl-N-methylcarbamates.     

Inhibitors of choline acetyltransferase as potential insecticides

Choline acetyltransferase (E.C.2.3.1.6) catalyses the synthesis of acetylcholine and is therefore a target for a new insecticide. We have prepared a variety of compounds, mainly choline analogues, as inhibitors of this enzyme. One of these, 2-isothiocyanatoethyltrimethylammonium iodide, has a K_i of 0.06 μM (K_m for choline is 150 μM ) and is apparently the most powerful inhibitor known for this enzyme. Although some of our compounds are insecticidal we believe, on the basis of electrophysiological studies, that they act, not on choline acetyltransferase, but on the acetylcholine receptor of the insect.