Quantitative structure-activity studies of benzoylphenylurea larvicides: II. Effect of benzyloxy substituents at aniline moiety against Chilo suppressalis Walker

The larvicidal activity of a series of N-2,6-difluorobenzoyl-N′-[4-(substituted benzyloxy)-phenyl]-ureas against nondiapause larvae of the rice stem borer, Chilo suppressalis Walker, was measured by a topical application method under conditions in which oxidative metabolism was inhibited by piperonyl butoxide. The effects of the substituted-benzyloxy moiety on variations in the activity were analyzed quantitatively using physicochemical substituent parameters and regression analysis. Results were compared with those found previously for N-2,6-difluorobenzoyl-N′-(4-substituted phenyl)-ureas, indicating that the electron-withdrawing property of the anilide substituents participates in determining the activity through the inductive effect. The hydrophobicity of the total anilide substituents favors activity, whereas the steric dimension in terms of the width lowers it. Although inhibition of new cuticle formation on cultured integument of diapausing larva could not be determined accurately for most of the compounds because of their limited solubility in the assay medium, inhibitory activity seemed related to larvicidal activity, as was the case for previously investigated simpler congeners.     

Quantitative structure-activity analysis of larvicidal 1-(substituted benzoyl)-2-benzoyl-1-tert-butylhydrazines against Chilo suppressalis

The larvicidal activity of a number of 1-(substituted benzoyl)-2-benzoyl–1 -ten-butylhydrazines against the rice stem borer (Chilo suppressalis Walk.) was measured. Variations in the activity were examined quantitatively using physico-chemical substituent and molecular parameters and regression analysis. The results indicated that the molecular hydrophobicity and the electron-withdrawing inductive/ field effect of ontho substituents are favourable to larvicidal activity. The bulkiness of substituents at the meta and para positions was unfavourable to activity, substitution at the para position being more unfavourable than that at the meta position in terms of van der Waals' volume. The 2,3–, 2,5- and 2,6-disubstitution patterns were also unfavourable to activity. Reductions in larvicidal activity caused by the 2,6-,- 2,3,5- and 2,3,4,5-substitutions were greater than those induced by the 2,3- and 2,5-disubstitutions. When the sum of contributions from favourable effects is greater than that from unfavourable effects, the larvicidal activity is expected to be superior to that of the unsubstituted compound.     

Quantitative structure-activity studies of insect growth regulators: XIX. Effects of substituents on the aromatic moiety of dibenzoylhydrazines on larvicidal activity against the beet armyworm Spodoptera exigua

Larvicidal activity against the beet armyworm, Spodoptera exigua (Hübner), was measured after topical treatment for a series of N-tert-butyl-dibenzoylhydrazines having various substituents in the benzoyl (A-ring) moiety closer to the tert-butyl group, the other benzoyl (B-ring) moiety being unsubstituted. The effects of substituents on the larvicidal activity were analyzed using the classical quantitative structure-activity relationship (QSAR) procedure. Introduction of hydrophobic substituents with a small volume into any position was favourable to activity. The existence of electron-withdrawing substituents at ortho positions was also favourable to activity. For multi-substituted compounds, physico-chemically unknown unfavourable factors were suggested to remain after separating common substituent effects derived from QSAR for mono-substituted analogues. With the exception of the unsubstituted compound RH-5849, the effect of substituents in the A-ring moiety on the larvicidal activity was similar to those found with the lepidopteran rice stem borer, Chilo suppressalis (Walker). The larvicidal activity of RH-5849 against S exigua was significantly lower than the value predicted from the correlation between activities against S exigua and C suppressalis. Topical treatment with piperonyl butoxide, a synergist inhibiting oxidative metabolism, slightly enhanced the larvicidal activity of RH-5849 against S exigua.     

Quantitative structure—activity studies of insect growth regulators. XI. Stimulation and inhibition of N-acetylglucosamine incorporation in a cultured integument system by substituted N-tert-butyl-N,N′-dibenzoylhydrazines

The ability to stimulate N-acetylglucosamine (GluNAc) incorporation in-vitro of a number of N-tert-butyl-N,N′-dibenzoylhydrazines having various substituents on both phenyl rings was measured in cultured integument excised from the rice stem borer (Chilo suppressalis Walker). The relationship between in-vitro and larvicidal potency was approximately linear. The substituent effects on variations in the potency were similar between in-vitro and larvicidal activities. An inhibitor of oxidative detoxication, piperonyl butoxide, had no synergistic effects on the in-vitro potency. The ability of some dibenzoylhydrazines to inhibit GluNAc incorporation at exposure periods longer than the optimum for stimulation was also measured in a similar cultured integument system. The relationship between the inhibitory and stimulatory potency indices was linear, indicating that the larvicidal activity of dibenzoylhydrazines is closely related to its ability to stimulate as well as to inhibit GluNAc incorporation into the larval cuticle.     

Quantitative structure-activity studies of insect growth regulators: XVIII. Effects of substituents on the aromatic moiety of dibenzoylhydrazines on larvicidal activity against the Colorado potato beetle Leptinotarsa decemlineata

Larvicidal activity against the Colorado potato beetle Leptinotarsa decemlineata (Say) was measured for a series of N-tert-butyl-dibenzoylhydrazines having various substituents on the benzoyl (A-ring) moiety nearer to the tert-butyl group, with the other benzoyl (B-ring) moiety being unsubstituted. The effects of these substituent on the larvicidal activity were analyzed using classical quantitative structure-activity relationship (QSAR) procedures. The effects of substituents on the A-ring moiety on larvicidal activity were entirely different from those against the lepidopteran rice stem borer Chilo suppressalis (Walker) previously reported. Position-specific steric and hydrophobic effects, as well as certain substitution patterns, were likely to participate in modifying the larvicidal activity. The activity of para-substituted compounds was generally lower than that of un-, ortho- and meta-substituted compounds. Most multi-substituted compounds showed an activity equivalent to or lower than that of the unsubstituted compound. Among 46 compounds tested, the 2-sec-butoxy analogue was most potent against L decemlineata, although this compound had previously been shown to be only weakly active against C suppressalis.     

Quantitative structure-activity relationships of antifungal N-phenylsuccinimides and N-phenyl-1,2-dimethylcyclopropanedicarboximides

The antifungal activity of 61 N-phenylsuccinimides and 16 N-phenyl-1,2-dimethylcyclopropanedicarboximides having various benzene ring substituents was determined against Botrytis cinerea by the agar medium dilution method. The structure-activity relationships were analyzed using such physicochemical substituent parameters as hydrophobic π, electronic σ⁰, steric E₈, and HB (hydrogen bonding) values with the multiple regression technique. The π values were derived from log P (octanol-water partition coefficient) values for the N-monosubstituted-phenylsuccinimide system. The hydrophobic effect is significant only for m-substitutents. The stronger the electron withdrawal and the smaller the steric dimensions of the ring substituents, the greater is the activity. When substituents are hydrogen bond acceptors, the effect is to lower the activity. These features are almost identical between two series of compounds.     

Quantitative structure-activity studies of pyrethroids: 12. Physicochemical substituent effects of meta-phenoxybenzyl α,α-disubstituted acetates on insecticidal activity

The insecticidal activity of a series of m-phenobenzyl esters of iso-valeric and tert-butylacetic acids, the α-position of which was substituted with one of alkyl, alkoxyalkyl, alkoxy, benzyl, phenyl, phenoxy, and anilino groups, was measured by injection into American cockroaches under synergistic conditions to suppress possible oxidative and hydrolytic metabolism. Their neuroexcitatory activity on nerve preparations excised from the cockroaches was measured by an extracellular recording technique. The activities of the analogous esters of cyclopropanecarboxylic acids with a substituted vinyl side chain were also measured. The insecticidal activity was quantitatively analyzed with physicochemical parameters for the α-substituent or its counterpart of the acid moiety. Variations in the activity were related parabolically to both the hydrophobicity and the length of the substituent. The activity of compounds, the α-substituent of which is either a substituted phenyl or a phenoxy group, was about 10 times that of compounds with “physicochemically equipvalent” aliphatic substituents. α-Substitution with ring-substituted anilino groups, but not with N-methyl groups, enhanced the activity about 25 times, but the vinylcyclopropane structure raised the activity to about 60 times that of physicochemically equivalent aliphatic noncyclopropane substituents. Variations in the insecticidal activity were closely related to those in the neuroexcitatory activity when hydrophobic and steric factors were separated. The steric factor in addition to the hydrophobicity seemed to be important in the transport process.     

Oxidative degradation of chlortoluron,propiconazole, and metalaxyl in suspension cultures of various crop plants

The metabolism of chlortoluron, (N′-(3-chloro-4-methylphenyl)-N,N-dimethylurea), propiconazole (1-[2-(2′,4′-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl-methyl]-1H-1,2,4-triazole), and metalaxyl (dl-N-(2,6-dimethylphenyl)-N-(2′-methoxyacetyl) alanine methyl ester) was investigated in suspension cultures of crop species for which differences in metabolism had been demonstrated at the intact plant level. Uptake and metabolism of chlortoluron by cultures of Italian rye-grass (Lolium multiflorum) was slow, the metabolites detected (42% of applied radioactivity after 13 days) being products of ring methyl oxidation and N-monodealkylation reactions. In sharp contrast, metabolism in a cotton (Gossypium hirsutum) suspension culture was extremely fast (72% after 4 hr) and was attributed to extensive N-didealkylation in addition to rapid ring methyl oxidation. This rate of metabolism also implied a very rapid uptake of chlortoluron by the cotton culture. ¹⁴C-labelled propiconazole became rapidly associated with cells of wheat (Triticum aestivum) and rice (Oryza sativa) following treatment of suspension cultures. Uptake was initially more rapid in the rice culture (36% of applied radioactivity after 8 h compared to 19% for wheat) which, together with a slower rate of metabolism, resulted in more unchanged propiconazole being associated with rice cells. On a parts-per-million basis these results indicated an apparent 10-fold accumulation of propiconazole in rice cells compared to 5-fold in the wheat culture. Propiconazole metabolite patterns were similar in cultures of both species and indicated side-chain hydroxylation as the principal pathway. Uptake of metalaxyl was slow in suspension cultures of both lettuce and potato (≅ 20% after 17 days). Subsequent metabolism was also slow but appeared to be limited by the poor rate of uptake. Both cultures were found to be similarly versatile with respect to metabolic attack on metalaxyl, which included ring methyl hydroxylation, aryl hydroxylation, ester cleavage, ether cleavage (O-dealkylation), and N-dealkylation (side-chain cleavage), the hydroxylation reactions being quatitatively the more important. The results for all three pesticides are compared to those obtained previously from studies with intact plants of the same species.     

Quantitative structure-activity studies of substituted benzyl chrysanthemates: 5. Physicochemical substituent factors and neurophysiological effects in knockdown and lethal activities against the house fly

Knockdown and lethal activities of meta- and para-substituted benzyl (1R)-trans-chrysanthemates against the house fly were measured under synergistic conditions using piperonyl butoxide as an inhibitor of oxidative metabolism and NIA 16388 as an inhibitor of hydrolytic degradation. The variations in these activities were quantitatively analyzed in terms of physicochemical substituent effects using electronic, hydrophobic, and steric parameters of the aromatic substituents, and regression analysis. The most significant parameter in determining these activities is the steric bulkiness represented by the van der Waals voluem, the effect of which is highly specific to substituent positions. The substituent effects on knockdown and lethal activities against the house fly are shown to correspond well, respectively, with those on the convulsive and lethal activities against the American cockroach. The relationship between these symptomatic activities against the house fly and the neurophysiological activities determined by using excised nerve cords from American cockroaches were also quantitatively analyzed. Each house fly symptomatic activity was found to be analyzable by a linear combination of the neuroexcitatory and neuroblocking activity indices when the transport factor was separated by using the hydrophobicity parameter.     

Toxicity and metabolism of carbaryl in the European corn borer

Larvae from two strains of the European corn borer, Ostrinia nubilalis (Hübner), were compared for differences in their tolerance and metabolism of carbaryl (1-naphthyl N-methylcarbamate). The Geneva strain was about twice as susceptible to carbaryl, but both Valley and Geneva borers converted carbaryl to oxidative metabolites at similar rates in vivo and in vitro. Maximum carbaryl-metabolizing activity was present in last-instar larvae, particularly in the fat body and gut tissues. However, the specific activity of gut homogenates was highest in the Geneva strain and the specific activity of fat body was highest in the Valley strain. Other differences in the mixed-function oxidase systems of gut and fat body were also found. The major metabolite in vivo and in vitro was hydroxymethyl carbaryl.     

Quantitative structure-activity study of herbicidal N-aryl-3,4,5,6-tetrahydrophthalimides and related cyclic imides

The quantitative relationship between structure and inhibitory activity against the root growth of sawa millet of 30 N-aryl-3,4,5,6-tetrahydrophthalimides and 88 related N-aryl cyclic imide compounds (3-aryl-1,5-tetramethylenehydantoins, 4-aryl-1,2-tetramethylenetriazolidine-3,5-diones, and their thiocarbonyl analogs) was analyzed by means of physicochemical parameters of the aryl substituents and regression analysis. The results showed that, in each series of these classes of compounds, the position-specific steric effects of aromatic substituents, as represented by Verloop's STERIMOL values, are highly important in determining the inhibitory potency of the compound.     

Metabolism of 2,2-dimethyl-2,3-dihydrobenzofuranyl-7 N-methyl-N-(2-toluenesulfenyl)carbamate in the housefly and white mouse

The metabolism of a new, selectively toxic derivative of carbofuran, 2,2-dimethyl-2,3-dihydrobenzofuranyl-7 N-methyl-N-(2-toluenesulfenyl)carbamate has been investigated. The selective toxicity between insect and mammal is due to differing pathways of metabolism. Houseflies appear peculiarly suited for the rapid liberation of the toxic agent, carbofuran, from N-(2-toluenesulfenyl) carbofuran in large amounts. Metabolism in the mouse is more complex and involves a series of oxidative and hydrolytic detoxication processes which do not result in the formation of carbofuran.     

Insecticidal,repellent and fungicidal properties of novel trifluoromethylphenyl amides

Twenty trifluoromethylphenyl amides were synthesized and evaluated as fungicides and as mosquito toxicants and repellents. Against Aedes aegypti larvae, N-(2,6-dichloro-4-(trifluoromethyl)phenyl)-3,5-dinitrobenzamide (1e) was the most toxic compound (24 h LC₅₀ 1940 nM), while against adults N-(2,6-dichloro-4-(trifluoromethyl)phenyl)-2,2,2-trifluoroacetamide (1c) was most active (24 h LD₅₀ 19.182 nM, 0.5 μL/insect). However, the 24 h LC₅₀ and LD₅₀ values of fipronil against Ae. aegypti larvae and adults were significantly lower: 13.55 nM and 0.787 × 10⁻⁴ nM, respectively. Compound 1c was also active against Drosophila melanogaster adults with 24 h LC₅₀ values of 5.6 and 4.9 μg/cm² for the Oregon-R and 1675 strains, respectively. Fipronil had LC₅₀ values of 0.004 and 0.017 μg/cm² against the two strains of D. melanogaster, respectively. In repellency bioassays against female Ae. aegypti, 2,2,2-trifluoro-N-(2-(trifluoromethyl)phenyl)acetamide (4c) had the highest repellent potency with a minimum effective dosage (MED) of 0.039 μmol/cm² compared to DEET (MED of 0.091 μmol/cm²). Compound N-(2-(trifluoromethyl)phenyl)hexanamide (4a) had an MED of 0.091 μmol/cm² which was comparable to DEET. Compound 4c was the most potent fungicide against Phomopsis obscurans. Several trends were discerned between the structural configuration of these molecules and the effect of structural changes on toxicity and repellency. Para- or meta- trifluoromethylphenyl amides with an aromatic ring attached to the carbonyl carbon showed higher toxicity against Ae. aegypti larvae, than ortho- trifluoromethylphenyl amides. Ortho- trifluoromethylphenyl amides with trifluoromethyl or alkyl group attached to the carbonyl carbon produced higher repellent activity against female Ae. aegypti and Anopheles albimanus than meta- or para- trifluoromethylphenyl amides. The presence of 2,6-dichloro- substitution on the phenyl ring of the amide had an influence on larvicidal and repellent activity of para- trifluoromethylphenyl amides.     

Insecticidal activity of N,N-diethyl-, N,N-dipropyl-, N,n-di-isopropyl-, and n,n-di-isobutylalkanamides against mosquito larvae

N,N-Diethyl-, N,N-dipropyl-, N,N-di-isopropyl, and N,N-di-isobutylalkanamides in which the acyl moiety ranged from C₈ to C₂₁ were synthesised, and their larvicidal activity was determined against the first-instar larvae of the southern house mosquito Culex quinquefasciatus Say. The four homologous series of amides generally showed an increase in their larvicidal activity as the carbon number in the acyl moiety of the amides increased, until the activity reached a maximum. Subsequently, an increment of carbon number resulted in declining activity in the higher homologues, until the activity disappeared. N,N-Diethyltetradecanamide, N,N-dipropylundecanamide, N,N-di-isopropylundecanamide, and N,N-di-isobutlynonanamide or -dodecanamide were the most active compounds in their respective homologous series of amides; however, they were less active than their analogous N,N-dimethylalkanamides previously studied.     

Triazophos resistance mechanisms in the rice stem borer (Chilo suppressalis Walker)

A field population of the rice stem borer (Chilo suppressalis Walker) with 203.3-fold resistance to triazophos was collected. After 8-generation of continuous selection with triazophos in laboratory, resistance increased to 787.2-fold, and at the same time, the resistance to isocarbophos and methamidophos was also enhanced by 1.9- and 1.4-fold, respectively, implying some cross-resistance between triazophos and these two organophosphate insecticides. Resistance to abamectin was slightly enhanced by triazophos selection, and fipronil and methomyl decreased. Synergism experiments in vivo with TPP, PBO, and DEM were performed to gain a potential indication of roles of detoxicating enzymes in triazophos resistance. The synergism results revealed that TPP (SR, 1.92) and PBO (SR 1.63) had significant synergistic effects on triazophos in resistant rice borers. While DEM (SR 0.83) showed no effects. Assays of enzyme activity in vitro demonstrated that the resistant strain had higher activity of esterase and microsomal O-demethylase than the susceptible strain (1.20- and 1.30-fold, respectively). For glutathione S-transferase activity, no difference was found between the resistant and the susceptible strain when DCNB was used as substrate. However, 1.28-fold higher activity was observed in the resistant strain when CDNB was used. These results showed that esterase and microsomal-O-demethylase play some roles in the resistance. Some iso-enzyme of glutathione S-transferase may involve in the resistance to other insecticides, for this resistant strain was selected from a field population with multiple resistance background. Acetylcholinesterase as the triazophos target was also compared. The results revealed significant differences between the resistant and susceptible strain. The V_max and K_m of the enzyme in resistant strain was only 32 and 65% that in the susceptible strain, respectively. Inhibition tests in vitro showed that I₅₀ of triazophos on AChE of the resistant strain was 2.52-fold higher. Therefore, insensitive AChE may also involved in triazophos resistance mechanism of rice stem borer.     

Comparison of dose responses and resistance ratios in four populations of the rice stem borer, Chilo suppressalis (Lepidoptera: Pyralidae), to 20 insecticides

BACKGROUND: Chemical control is a major strategy for suppressing the rice stem borer, Chilo suppressalis (Walker). Owing to their high toxicity and increasing resistance development in the target insect, many insecticides will be phased out entirely in 2007 in China. Alternatives with relatively low toxicity are urgently needed to replace traditional chemicals for rice stem borer control. In this study, the authors examined four field populations of C. suppressalis for their toxicological responses to more than 20 insecticides, including a few low-toxicity organophosphates and many novel pesticides. Interpopulation resistance levels to 12 conventional insecticides were also compared. RESULTS: Based on LD(50) values, the rice stem borer was most sensitive to avermectins and fipronil (LD(50) < 1 ng larva(-1)). The stem borers exhibited the least sensitivity to endosulfan (LD(50) > 100 ng larva(-1)) and monosultap (LD(50) > 1000 ng larva(-1)). Insect growth regulators and chitin synthase inhibitors showed great efficacy against C. suppressalis, especially against populations that had developed resistance to conventional insecticides. Four field populations showed variable tolerance levels to many insecticides. LYG05 was the most susceptible population, only with a low level of resistance to monosultap (RR = 6.6). NC05 and GL05 populations exhibited intermediate tolerance levels with RR values up to 20.4 and 52.8 respectively. RA05 was the most resistant population to many insecticides, with resistance ratios up to 76.2. CONCLUSION: The results from this study provide valuable information for selection and adoption of new alternative insecticides and for resistance management of the rice stem borer.     

Absorption,translocation and metabolism of the herbicide naproanilide in tobacco

Naproanilide [2-(2-naphthyloxy)propionanilide] has a high activity against dicotyledonous weeds in rice fields, but is very safe to rice. This study was designed to clarify the absorption and translocation of radiolabelled naproanilide in tobacco plants and the metabolism in tobacco callus. The results indicated that naproanilide is translocated easily to the upper part of tobacco plants. Distribution of radioactivity in tobacco plants at the 7th day was shown to be 0.88, 0.24 and 0.03%, and at the 14th day 1.71, 1.86 and 2.32% of the total activities of [¹⁴C]naproanilide in root, stem and leaf, respectively. When compared to earlier results obtained with rice, the translocation rate in tobacco is much higher and might therefore contribute a possible mechanism of herbicidal selectivity. Metabolites including NOP [2-(2-naphthyloxy)propionic acid], NOPM [methyl 2-(2-naphthyloxy)propionate], 2-naphthol, 2,3-naphthalenediol, 2,6-naphthalenediol, 2,7-naphthalenediol and 2-hydroxy-1,4-naphthoquinone were identified in tobacco callus by co-chromatography.     

Structure-activity study of herbicidal N-chloroacetyl-N-phenylglycine esters

N-Chloroacetyl-N-phenylglycine esters were shown to exert various degrees of growth inhibiting activity against young shoots of annual grasses. The activity against the rice plant and barnyard-grass was determined for 58 derivatives where either the aromatic substituent or ester moiety was modified. The structure-activity relationships were analyzed using physicochemical parameters of the molecule such as log P, σ, and E_s, and regression analysis. By comparing the correlations derived for the rice plant and barnyard-grass, the selectivity in herbicidal activity is discussed.     

二化螟寄主选择行为与种群消长机制的研究进展

二化螟[Chilo suppressalis(Walker)]是一种钻蛀性害虫,具有食性杂、越冬场所多、转株为害等特点,其种群数量近年来呈回升趋势,危害逐年加重。二化螟对寄主存在明显的选择行为,其主要寄主之一水稻由于品种更替、耕作制度变更及气候变化等因素对二化螟种群发生规律产生了一些新的影响,给害虫防治工作带来了许多新问题。研究和了解二化螟的寄主选择规律及其机制,以及影响其种群动态的因素是有效调控二化螟种群的重要前提。本文就二化螟寄主选择行为与机制及其在水稻上种群消长影响因素等的研究概况进行综述报道,旨在更好地为二化螟的综合防治提供指导。