Defining the resistance risk of the new powdery mildew fungicide quinoxyfen

The new powdery mildew fungicide quinoxyfen belongs to the novel quinoline class of chemistry. Although its biochemical mode of action is unknown, quinoxyfen does not act in the same way as other cereal fungicides. It is a systemic protectant which inhibits the early stages of mildew infection on a wide range of crops, and provides season-long protection from a single early-season spray applied around GS 31. The base-line sensitivity profile of quinoxyfen was defined for barley powdery mildew (Erysiphe graminis f.sp. hordei) from over 340 field isolates collected from different parts of the UK from 1991 onwards. Sensitivities ranged from <0·0001→0·16 mg litre^-1 with a mean of 0·003 mg litre^-1. Current work is extending the base-line sensitivity studies to wheat powdery mildew (E. graminis f.sp. tritici), and includes isolates from European trials, but so far this new data set has shown no differences from barley powdery mildew. Quinoxyfen-resistant mutants were generated in the laboratory, and some similar resistant strains were obtained from treated field crops. These laboratory and field strains were always defective, in some way, for sporulation and, curiously, all required the presence of quinoxyfen for survival in culture. Attempts to generate resistant mutants that sporulated normally were unsuccessful. These studies suggested that the resistance risk for quinoxyfen is low. The recommended anti-resistance strategy accompanying introduction of quinoxyfen avoids seed treatments and late-season applications. Instead, a single early (GS 31) treatment using either pre-formulated mixtures or alternating with a fungicide with different mode of action is recommended. This strategy will be supported by continued monitoring of wheat and barley powdery mildew. ©1997 SCI     

Ribavirin, a nucleoside with potential insecticidal activity

BACKGROUND: The triazole-based antiviral nucleoside ribavirin exhibited significant in vitro insecticidal effects against Spodoptera litura, a finding that has prompted further investigations into its in vivo insecticidal properties and mode of action against this insect pest. RESULTS: Ribavirin showed delayed insecticidal effects on third-instar larvae of S. litura at a concentration of 1 mg mL⁻¹. When incorporated into an artificial diet, ribavirin caused various effects, depending on the concentration used. Compared with controls, food intake was lower, larval growth was reduced and larval development prolonged. Pupae weight was reduced, and adult morphology was also affected. Relative to the untreated group, treated groups showed higher mortality at larval and pupal stages, which was generally caused by moult disruption. Results of this study with ribavirin resemble those found in treatment with insect growth regulators. CONCLUSION: This work shows that ribavirin merits further study as a lead compound in a novel class of potential insect control agents or for managing field populations of Lepidoptera pests on cruciferous crops. Copyright © 2012 Society of Chemical Industry     

Aminopyrifen,a novel 2-aminonicotinate fungicide with a unique effect and broad-spectrum activity against plant pathogenic fungi

Aminopyrifen is a novel 2-aminonicotinate fungicide with unique chemistry and a novel mode of action. The fungicide showed high antifungal activity mainly against Ascomycetes and its related anamorphic fungi under in vitro and pot conditions (EC₅₀ values: 0.0039–0.23 mg/L and 1.2–12 mg/L, respectively). The active ingredient strongly inhibited germ-tube elongation of Botrytis cinerea below 0.1 mg/L and invasion into a plant. The compound exhibited no cross-resistance to commercial fungicides in B. cinerea. The antifungal agent showed high preventive efficacy and translaminar action. In the field, aminopyrifen controlled gray mold and powdery mildew at 150 mg/L. Our findings suggest that aminopyrifen is useful for protecting crops from various plant pathogens.     

Design,synthesis and acaricidal activity of novel strobilurin derivatives containing pyrimidine moieties

BACKGROUND: The intermediate derivatisation method based on bioisosteric replacement led to the discovery of the lead strobilurin compound 5a. To produce new strobilurin analogues with improved activity, a series of substituted pyrimidines were synthesised and bioassayed. RESULTS: The compounds were identified by ¹H NMR, IR, MS and elemental analysis. The highly active compound 5g was studied by X‐ray diffraction. Preliminary bioassays demonstrated that some of the title compounds exhibited excellent acaricidal activity against Tetranychus cinnabarinus (Boisd.) at 10 mg L^?1. The relationship between structure and acaricidal activity is reported. CONCLUSION: The present work demonstrates that strobilurin derivatives containing pyrimidine moieties can be used as possible lead compounds for developing novel acaricides. Copyright © 2010 Society of Chemical Industry     

新型哌啶-4-醇衍生物的合成及生物活性

发现具有新作用方式的农药对于现代作物保护至关重要。本研究以哌啶醇和邻苯二酚为起始原料，经5步反应制备得到了一系列新型的哌啶-4-醇衍生物，并通过核磁共振氢谱、碳谱和高分辨质谱确认其结构。生物活性测试结果表明，部分目标化合物在25 mg/L质量浓度下表现出良好的根结线虫Meloidogyne incognita抑制活性。此外，在500 mg/L质量浓度下，大部分化合物对黏虫Pseudaletia separata Walker表现出因拒食效应所致的体重减轻。     

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.     

The herbicide flamprop-M-methyl has a new antimicrotubule mechanism of action

BACKGROUND: The herbicidal mode of action of flamprop‐M‐methyl [methyl N‐benzoyl‐N‐(3‐chloro‐4‐fluorophenyl)‐D ‐alaninate] was investigated. RESULTS: For initial characterization, a series of bioassays was used, which indicated a mode of action similar to that of mitotic disrupter herbicides. Cytochemical fluorescence studies, which included monoclonal antibodies against polymerized tubulin, were applied to elucidate effects on mitosis and microtubule assembly in maize roots. When seedlings were root treated with 50 µM of flamprop‐M‐methyl, cell division activity in meristematic root tip cells ceased within 4 h. The compound severely disturbed the orientation of spindle and phragmoblast microtubules, leading to defective spindle and phragmoblast structures. Cortical microtubules were only slightly affected. In late anaphase and early telophase cells, phragmoblast microtubules were disorganized in multiple arrays that hampered regular cell plate deposition in cytokinesis. Microtubules of the spindle apparatus were found attached to chromosomal kinetochores, but did not show regular organization associated with a zone of microtubule‐organizing centres at the opposite ends of the cell. On account of this loss of spindle organization, chromosomes remained in a condensed state of prometaphase or metaphase. Unlike known microtubule disrupter herbicides, flamprop‐M‐methyl and its biologically active metabolite flamprop did not inhibit soybean tubulin polymerization to microtubules in vitro at 50 µM . In contrast, soybean plants responded sensitively to the compounds. CONCLUSION: The results indicate that flamprop‐M‐methyl is a mitotic disrupter herbicide with a new antimicrotubule mechanism of action that affects orientation of spindle and phragmoblast microtubules, possibly by minus‐end microtubule disassembly. Copyright © 2008 Society of Chemical Industry     

Fungicidal activity of substituted quinoxalines

Twenty substituted quinoxalines based on the structure of 6 (or 7)-methyl-3-phenyl-1, 2-dihydroquinoxalin-2-one, a fungicidally active photodegradation product of quinomethionate, were synthesised. Eleven of these compounds had ED₅₀ values, as protectant sprays against Podosphaera leucotricha, of 0.1 mmol or less; these compounds had an aromatic substituent at the 3-position of the quinoxaline ring. They were less active as protectant leaf dips against Erysiphe graminis f. sp. hordei than against Podosphaera leucotricha; none showed any systemic activity as a soil-applied treatment against Podosphaera leucotricha. One compound was more active than quinomethionate as an eradicant spray. In spore germination tests on fungi from different taxonomic groups, the quinoxaline derivatives were active against only one basidiomycete (Uromyces fabae), whereas quinomethionate showed a broad spectrum of activity. The possible significance of this difference in spectrum of activity with respect to the mode of action is discussed.     

Insecticidal activity against Aedes aegypti of m-pentadecadienyl-phenol isolated from Myracrodruon urundeuva seeds

BACKGROUND: Myracrodruon urundeuva Fr. Allemao is a common tree in the Caatinga that has been widely used for various medical purposes. Previous studies showed that the ethanol seed extract of M. urundeuva has potent activity against the larval stage of the dengue vector Aedes aegypti. Given this potential insecticidal activity, bioguided separation steps were performed in order to isolate the active compound(s). RESULTS: The isolation process resulted in only one active chemical compound, identified by infrared spectroscopy and mass spectrometry as m-pentadecadienyl-phenol. This compound presented potent larvicidal and pupicidal activity (LC₅₀ 10.16 and 99.06 µg mL⁻¹ respectively) and great egg hatching inhibitory activity (IC₅₀ 49.79 µg mL⁻¹). The mode of action was investigated through observations of behavioural and morphological changes performed in third-instar larvae treated with m-pentadecadienyl-phenol solution after 1, 6, 12, 16 and 20 h of exposure. Some changes were observed as flooding of the tracheal system, alterations in siphonal valves and anal gills and lethargy, probably caused by the strong anticholinesterasic activity reported previously. CONCLUSION: The compound isolated from M. urundeuva seeds, m-pentadecadienyl-phenol, showed potent activity against immature stages of dengue vector, Ae. aegypti, being considered the main larvicidal principle. Copyright © 2012 Society of Chemical Industry     

Design, semisynthesis and insecticidal activity of novel podophyllotoxin derivatives against Brontispa longissima in vivo

In an attempt to find the effective phytopesticides, a series of novel podophyllotoxin derivatives were firstly synthesized and preliminarily tested for their antifeedant and insecticidal effects against the fifth-instar larvae of Brontispa longissima. The different antifeedant and insecticidal activity ranges of compounds 3a-l showed that variations of NR₁R₂ groups in the 4-position of podophyllotoxin skeleton markedly affected the activity profiles of this compound class, and some important SAR information has been revealed from it. To clarify their mode of action of insecticidal activity, the docking models as well as tubulin inhibitory effect of representative compound 3i were also investigated, and the result indicated that the insecticidal activity of these compounds was due to the tubulin inhibitory effect of these derivatives, thereby possibly providing some useful information for rational designs of novel podophyllotoxin-based insecticides.     

The origins of selectivity and performance of a new pre-emergence bleaching herbicide,WL 110547. Part II: Plant and environmental factors influencing biological activity

Pre-emergence applications of the novel tetrazole herbicide WL 110547 control a number of economically important grass and broad-leaved weed species in small grain cereals. To assess the influence of plant and environmental factors on the biological performance of WL 110547, a series of tests were carried out under controlled conditions and, where appropriate, comparisons were made with field observations. When presented with the maximum opportunity for compound uptake in the absence of soil, differences in the degree of susceptibility to WL 110547 were observed amongst both monocotyledonous and dicotyledonous species, although the latter group generally showed higher levels of phytotoxicity. This species susceptibility to WL 110547 was unaffected by temperature. Increasing the sowing depth in soil decreased the level of effect of WL 110547 on a number of monocotyledonous species, although small-seeded species (e.g. blackgrass, annual meadow grass), emerging from deep in the soil profile, subsequently developed levels of phytotoxicity comparable to, or even greater than, shallow-planted seedlings. This was attributed to less vigorous seedlings, emerging from depth, that were unable to regenerate new tissue and grow away from a treated soil layer. Reduced growth rates of wild oat, blackgrass and speedwell, induced by low temperatures, also increased the phytotoxicity of WL 110547. Furthermore, applications of WL 110547 during seedling emergence maximised herbicide effect, as did seedling emergence through moist rather than dry soil. The results are discussed in relation to the mobility of the herbicide in soil, the mode of action of WL 110547, its availability to the plant and the duration of contact between emerging shoot and treated soil layer.     

靶向蜕皮激素受体的新型4,5,6,7-四氢-2H-吲唑酰肼类衍生物的设计、合成及杀虫活性

为了发现结构新颖的昆虫生长调节剂,以蜕皮激素受体(EcR)为靶标,以课题组发现的高活性化合物C(N-(4-(叔丁基)苯基)-2-苯基-2,4,5,6,7,8-六氢环庚基[C]吡唑-3-甲酰胺)为先导化合物,利用活性亚结构拼接的方法,设计合成了25个未见文献报道的新型4,5,6,7-四氢-2H-吲唑酰肼类衍生物,其结构经...     

Guanidinium and amidinium fungicides: A new class of carbocation mimetic ergosterol biosynthesis inhibitors

A novel class of chemical has been designed with the aim of inhibiting the Δ¹⁴-reductase and Δ⁸-Δ⁷-isomerase enzymes in the ergosterol biosynthesis pathway in fungi. Use was made of knowledge about the mechanisms of both enzymes and the mode of action of known, fungicidal inhibitors of these enzymes. Pioneer examples have been synthesised and have been demonstrated to be potent inhibitors of ergosterol biosynthesis in Ustilago maydis (DC) Corda, acting in the same manner as the commercial fungicide fenpropimorph. They also showed excellent fungicidal activity against Erysiphe graminis DC f. sp. hordei Marchal (powdery mildew of barley) and Puccinia recondita Rob. ex Desm. (wheat leaf rust) in in-vivo glasshouse tests. Using these compounds as a starting point, systematic structural variation has been carried out. Testing of a wide range of analogues at high volume confirms the potential of this class of compound to control mildew and rust pathogens at levels comparable to those of the standards. Correlation of in-vivo and enzymatic data is good and the structure-activity relationship developed for this series of compounds closely parallels that found for the morpholine/piperidine class of fungicides, suggesting a common mode of action.     

Review A Review of the Mechanisms Involved in the Action of Phosphine as an Insecticide and Phosphine Resistance in Stored-Product Insects

Phosphine gas has been used world-wide for more than four decades as an ideal fumigant for disinfestation of stored grains and other commodities. Its use as a safe fumigant of stored products has become even more important with recent restrictions on the production of the only alternative, methyl bromide. Widespread resistance to phosphine has emerged in several species of stored-product insects in many countries, which in some instances may have caused control failures. Chemically, phosphine is a strong reducing agent and biological redox systems, especially the components of the mitochondrial electron transport chain, are probably the site of its action in insects. The oxidation of phosphine could produce reactive phosphorylating species and interactions of phosphine with biological redox systems have been reported to cause generation of highly reactive oxyradicals. This appears to be the basis of phosphine toxicity to insects, which differs from that of respiratory inhibitors such as hydrogen cyanide. Phosphine-resistant strains of several species of stored-product insects have been reported to absorb very small amounts of the compound compared to their susceptible counterparts. This reduced uptake in resistant insects appears to result from respiratory exclusion of phosphine. The overall mechanism of resistance also involves a detoxification process. Despite the likely involvement of oxyradicals in the insecticidal action of phosphine, the level of anti-oxidant enzymes in resistant insects is apparently not higher than that in their susceptible counterparts. The reduced uptake of the compound might be due either to the presence of a phosphine insensitive target site or to a membrane-based efflux system that excludes phosphine gas in resistant insects. Studies have indicated the oxygen uptake in mitochondrial preparations from susceptible and resistant insects to be equally sensitive to inhibition by phosphine in vitro. The nature of the phosphine-exclusion system in resistant insects has not been fully elucidated. The possibilities of controlling resistant insects with phosphine and prospects for developing new alternative fumigants are also discussed. © 1997 SCI.     

The action of pyrethroids in the insect central nervous system. I. Features of molecular structure associated with toxicity to cockroaches and to their giant fibre axons

To investigate relationships between the molecular structure of pyrethroids and their mode of action, toxicities to adult male Periplaneta americana by topical application and injection were compared with toxicities to their giant fibre nerve axons. From the tests against intact insects it was concluded that: (i) although ED₅₀S ranged from 0.04 to 65 μg/insect, each compound was equally toxic, with one exception, when administered by either route; (ii) esters of (1 R)-cis- were more toxic than esters of the corresponding (1 R)-trans-3-substituted-2, 2-dimethylcyclopropanecarboxylic acids; (iii) α-cyano-3-phenoxybenzyl esters were more toxic than the corresponding 3-phenoxybenzyl esters; (iv) changes in the alcoholic component of some compounds (particularly trans-isomers of esters of 5-benzyl-3-furylmethanol and esters of α-cyano-3-phenoxybenzyl alcohol) affected a recovery phase in their ED₅₀/time curves more than changes in the acid component; (v) the amount of recovery was positively correlated with molecular polarity. The concentration required to decrease the amplitude of the action potential of giant fibres by 30% in 1 h ranged from 0.26 μM for the most active compound to 100 μM for the least active. There was no clear relationship between neurotoxicity and toxicity to whole insects and little association between neurotoxicity and features of molecular structure. Neurotoxicity was, however, positively correlated with polarity. Giant fibre axons seem unlikely to be critical sites of action of pyrethroids.     

The unique role of halogen substituents in the design of modern agrochemicals

The past 30 years have witnessed a period of significant expansion in the use of halogenated compounds in the field of agrochemical research and development. The introduction of halogens into active ingredients has become an important concept in the quest for a modern agrochemical with optimal efficacy, environmental safety, user friendliness and economic viability. Outstanding progress has been made, especially in synthetic methods for particular halogen‐substituted key intermediates that were previously prohibitively expensive. Interestingly, there has been a rise in the number of commercial products containing ‘mixed’ halogens, e.g. one or more fluorine, chlorine, bromine or iodine atoms in addition to one or more further halogen atoms. Extrapolation of the current trend indicates that a definite growth is to be expected in fluorine‐substituted agrochemicals throughout the twenty‐first century. A number of these recently developed agrochemical candidates containing halogen substituents represent novel classes of chemical compounds with new modes of action. However, the complex structure–activity relationships associated with biologically active molecules mean that the introduction of halogens can lead to either an increase or a decrease in the efficacy of a compound, depending on its changed mode of action, physicochemical properties, target interaction or metabolic susceptibility and transformation. In spite of modern design concepts, it is still difficult to predict the sites in a molecule at which halogen substitution will result in optimal desired effects. This review describes comprehensively the successful utilisation of halogens and their unique role in the design of modern agrochemicals, exemplified by various commercial products from Bayer CropScience coming from different agrochemical areas. Copyright © 2009 Society of Chemical Industry     

The synthesis of potential insecticides designed to bind to the acetylcholine receptor

A variety of compounds designed to bind to the acetylcholine receptor, a largely unexploited target for new insecticides, have been prepared. These are related to either the isothiocyanates prepared previously in our laboratory, which probably bind to the receptor, or to nereistoxin, which is known to do so. Many of the compounds are insecticidal, and electro-physiological studies on a candidate compound, N,N-dimethyl-3-thiocyanato-2-(thiocyanatomethyl)propionamide, suggest they may have the predicted mode of action.     

Toxicity of spiromesifen to the developmental stages of Bemisia tabaci biotype B

BACKGROUND: Spiromesifen is a novel insecticidal/acaricidal compound derived from spirocyclic tetronic acids that acts effectively against whiteflies and mites via inhibition of acetyl‐CoA‐carboxylase, a lipid metabolism enzyme. The effects of spiromesifen on the developmental stages of the whitefly Bemisia tabaci (Gennadius) were studied under laboratory conditions to generate baseline action thresholds for field evaluations of the compound. RESULTS: Adult B. tabaci mortality rate after spiromesifen treatment (5 mg L^?1) was 40%. Treatment with 0.5 mg L^?1 reduced fecundity per female by more than 80%, and fertility was almost nil. LC₅₀ for eggs was 2.6 mg L^?1, and for first instar 0.5 mg L^?1. Scanning electron microscopy revealed that eggs laid by treated adult females had an abnormally perforated chorion, and females were unable to complete oviposition. Light and fluorescent microscopy showed significantly smaller eggs following treatment, and smaller, abnormally formed and improperly localized bacteriomes in eggs and nymphs. The number of ovarioles counted in females treated with 5 mg L^?1 was significantly reduced. Spiromesifen showed no cross‐resistance with other commonly used insecticides from different chemical groups, and resistance monitoring in Israel showed no development of field resistance to this insecticide after 1 year of use. CONCLUSION: The strong effect on juvenile stages of B. tabaci with a unique mode of action and the absence of cross‐resistance with major commonly used insecticides from different chemical groups suggest the use of spiromesifen in pest and resistance management programmes. Copyright © 2008 Society of Chemical Industry     

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