Quantitative structure-activity studies of substituted benzyl chrysanthemates: 2. Physicochemical substituent effects and neurophysiological and symptomatic activities against American cockroaches     

Shoji Nakagawa  Nobuyuki Okajima  Keiichiro Nishimura  Toshio Fujita  Minoru Nakajima 《Pesticide biochemistry and physiology》1982,17(3):259-270

The substituent effects on the symptomatic and neurophysiological activities of a number of substituted benzyl (1R)-trans-chrysanthemates against American cockroaches were quantitatively analyzed using electronic, hydrophobic, and steric parameters. The effects were shown to be highly specific to substituent positions except for those on the neuroblocking activity. Steric effect of substituents represented by van der Waals volume was found to play the most significant role in determining the variation in each activity. Peculiar substituent effects depending upon the bulkiness and position of substituents, which had been observed in the toxicity of this class of compounds, can be rationalized by the present analysis indicating that the optimum van der Waals volume of substituents is largest at the ortho and smallest at the para position.  相似文献   

Quantitative structure-activity study of insecticidal 2-methoxy-5-(substituted-phenyl)-1, 3, 2-oxazaphospholidine 2-sulfides against Musca domestica L. by topical application     

Akinori Hirashima  Yutaka Yoshii  Ryuko Takeya  Morifusa Eto 《Pest management science》1992,35(3):223-226

The quantitative relationship between the structure of 2-methoxy-5-(substituted-phenyl)-1, 3, 2-oxazaphospholidine 2-sulfides (5-PMOS) and their insecticidal activity against the house fly. Musca domestica L., was analyzed using reported physicochemical parameters and regression analysis. The electronic nature of the substituent on the phenyl group of 5-PMOS has the most significant effect on the activity, followed by hydrophobic and steric effects; the optimum value of Σρ is zero and the more hydrophobic the substituents on the phenyl group, the higher the insecticidal activity. The plots of observed pLD₅₀, values against calculated pLD₅₀ values for compounds having substituents in the ortho-position deviated downwards from those of compounds having substituents at the meta and/or para positions. This ortho-effect, which reduces the insecticidal activity of compounds having substituents at the ortho-position, was expressed by a dummy parameter D, which has the value 2 for di-ortho-substituted derivatives, 1 for mono-ortho-substituted derivatives and zero for others. Thus, the highest activity was obtained for 2-methoxy-5-phenyl-1, 3, 2-oxazaphospholidine 2-sulfide, and the activity was decreased by the introduction of any substituents on the phenyl group.  相似文献   

Acute and delayed neurotoxicity of leptophos analogs     

Robert L. Metcalf  B.Magnus Francis  Robert A. Metcalf  Larry G. Hansen 《Pesticide biochemistry and physiology》1983,20(1):57-66

Nineteen O-halogenated-phenyl O-methyl phenylphosphonothionates were evaluated for acute toxicity (LD₅₀) to the female house fly Musca domestica L. and to the male Swiss white mouse, and for delayed neurotoxicity to the White Leghorn hen. The electron-withdrawing power of the phenyl substituents (Σσ^? values) correlate with the LD₅₀ values to house fly and mouse, with departures from linearity attributable to the steric hindrance of di-ortho-Cl substitution and by variations in the accessibility of the anionic site of acetylcholinesterase in the two species. The relationship with delayed neurotoxicity is less predictable although it clearly depends on suitable electron-withdrawing capacity. Delayed neurotoxicity also relates to a high degree of lipophilicity and prolonged residence time of the inhibitor in the nerve axon.  相似文献   

Quantitative structure—activity relationships of light-dependent herbicidal 4-pyridone-3-carboxanilide derivatives II. Substituent effects of anilide and pyridone moieties     

Hirokazu Osabe  Yasuo Morishima  Yukihisa Goto  Kazuhisa Masamoto  Yoshiaki Nakagawa  Toshio Fujita 《Pest management science》1992,34(1):27-36

The variations in the light-dependent herbicidal activity against Echinochloa oryzicola of a number of 4-pyridone-3-carboxanilides with various substituents on the anilide and pyridone rings have been examined by use of physicochemical substituent parameters and regression analysis. The effects of substituents of the anilide ring were such that the activity was related parabolically not only with the substituent hydrophobicity (π) but also with the steric bulk parameter (E_s) of the bulkier ortho substituent. The effect of substituents at the 1-position of the pyridone ring was analysed with steric(STERIMOL L and B₅) and electronic(γ₁) parameters. That of substituents at the 5-position of the pyridone ring was explained by a parabolic function of a steric (MR) parameter. Analyses of the activity of 105 analogs confirmed that our previous selection of a candidate compound in this series for field trials was indeed appropriate in terms of physicochemical substituent effects.  相似文献   

Insecticidal activity and microsomal metabolism of biooxidizable lindane analogs     

Makoto Kiso  Masahide Nohta  Keiji Tanaka  Norio Kurihara  Toshio Fujita  Minoru Nakajima 《Pesticide biochemistry and physiology》1977,7(4):341-348

The insecticidal activity of lindane analogs, in which some chlorine atoms were replaced by other groups susceptible to microsomal oxidative metabolism, was determined against mosquitos, house flies, and German cockroaches. When tested with a synergist, piperonyl butoxide, one of the methylthio analogs was as active as lindane, whereas several others were also highly active. By examining the ratio of synergized and unsynergized LD₅₀ values (synergistic ratio value), the highly insecticidal methylthio, methoxy, and methyl analogs appear to undergo metabolic detoxication effectively in house flies. By means of in vitro metabolism experiments using microsomal fraction from house fly abdomen, the methoxy, ethoxy, and methylthio analogs were shown to be metabolized rapidly at similar rates. The synergized insecticidal activities of these compounds against various insect species relate linearly with each other, suggesting that the oxidative degradation is inhibited by the synergist to a similar extent and that the transport process to the site of action is not a limiting factor in determining the relative insecticidal activity.  相似文献   

Quantitative structure—activity studies of some octopaminergic agonists against Periplaneta americana     

Akinori Hirashima  Eiji Taniguchi  Morifusa Eto 《Pest management science》1995,43(4):311-315

The quantitative relationship between the structure of 2-(arylimino) thiazolidines (AITs), arylethanolamines (AEAs) and 2-(arylalkylamino)-2-thi-azolines (AATs) and their octopamine (OA)-agonist activities against the ventral nerve cord of American cockroach, Periplaneta americana L., was analysed using reported physicochemical parameters and regression analysis. The electronic nature of a substituent was the most important factor for AAT, followed by the hydrophobic effects: the more electron-donating and the more hydrophobic the substituent, the greater the activity. The hydrophobic nature of a substituent in AEA was the most important factor, followed by the steric effects: the more hydrophobic the substituent, the greater the activity. The more electron-donating the substituent of AIT, the greater the activity.  相似文献   

Genetic studies on glutathione-dependent reactions in resistant strains of the house fly,Musca domestica L     

N. Motoyama  W.C. Dauterman  F.W. Plapp 《Pesticide biochemistry and physiology》1977,7(5):443-450

Genetic studies of glutathione-dependent reactions were conducted with a diazinon-resistant house fly strain in which resistance is controlled primarily by genes on chromsome II. The resistant strain was crossed with a susceptible strain which had mutant markers on chromosomes II, III, and V, and the F₁ was backcrossed to the susceptible strain. Glutathione transferase activities of the resultant eight phenotypes were measured using 3,4-dichloronitrobenzene, methyl iodide, and γ-benzene hexachloride as substrates. High levels of all these activities are controlled by gene(s) on chromosome II. Further analysis was made by introducing diazinon resistance into a susceptible strain via genetic crossing-over. Intermediate activity levels for 3,4-dichloronitrobenzene and methyl iodide conjugations were introduced along with intermediate levels of resistance. Assays of individual flies of the synthesized strain revealed they were heterogeneous for glutathione-dependent activities, consisting of individuals with low, intermediate, and high transferase activity. Based on these results, high levels of the glutathione-dependent enzymes are not a major biochemical mechanism responsible for diazinon resistance. It was also demonstrated that glutathione S-aryltransferase and S-alkyltransferase in the house fly, as measured with 3,4-dichloronitrobenzene and methyl iodide, are inseparable genetically and may, therefore, be the same enzyme.  相似文献   

Acetylcholinesterase inhibition by nootkatone and carvacrol in arthropods     

J.A. Anderson  J.R. Coats 《Pesticide biochemistry and physiology》2012,102(2):124-128

The essential oils from many botanicals have been screened for insecticidal activity. Two constituents of the Alaskan yellow cedar tree, the monoterpenoid carvacrol and the sesquiterpenoid nootkatone, both are toxic against several arthropods. The mode of action through which nootkatone and carvacrol exert their insecticidal activity remains uncertain. It has been hypothesized that they may inhibit acetylcholinesterase enzyme activity. The degree of acetylcholinesterase inhibition of carvacrol and nootkatone was compared to that of carbaryl, a known acetylcholinesterase inhibitor, in the house fly (Musca domestica), yellow fever mosquito (Aedes aegypti), American dog tick (Dermacentor variabilis) and American cockroach (Periplaneta americana). The concentration of carbaryl, at which 50% of the acetylcholinesterase activity was inhibited (IC₅₀), was less than 2 μM in all four arthropod models. Carvacrol was observed to cause slight inhibition of the acetylcholinesterase enzyme in house flies, ticks and cockroaches, but it did not inhibit the mosquito acetylcholinesterase enzyme. Nootkatone did not inhibit the acetylcholinesterase enzyme in any of the four arthropod models tested. From this study, we conclude that the acetylcholinesterase inhibition is not likely the primary mode of action for insecticidal activity by nootkatone or carvacrol.  相似文献   

Comparative insecticidal activities and metabolic rates of lindane and its hexadeuterio-analog     

Keiji Tanaka  Norio Kurihara  Minoru Nakajima 《Pesticide biochemistry and physiology》1976,6(4):386-391

Hexadeuterio-lindane(γ-BHC-d₆) was several times as toxic as lindane against the mosquito (Culex pipiens pallens), house fly (Musca domestica), German cockroach (Blattella germanica) and American cockroach (Periplaneta americana). The neuroexcitatory activity of these two compounds did not differ. Lindane was considerably synergized by piperonyl butoxide, but lindane-d₆ was not. A large isotope effect was observed in the in vivo breakdown of lindane-d₆. Thus, the intrinsic toxicities of both compounds are equivalent. The difference in insecticidal activity seems to be due to the different rates of detoxifying biodegradation caused by the kinetic deuterium isotope effect.  相似文献   

Dimethoxypyrimidines as novel herbicides. Part 4. Quantitative structure–activity relationships of dimethoxypyrimidinyl(thio)salicylic acids     

Yukio Nezu  Nobuhide Wada  Fumitaka Yoshida  Takeshige Miyazawa  Tsutomu Shimizu  Toshio Fujita 《Pest management science》1998,52(4):343-353

The activity of a number of O-(4,6-dimethoxypyrimidin-2-yl)salicylic acids and their thio analogs inhibiting acetolactate synthase (ALS) preparation was measured. The effects of substituents on the salicylic-benzene ring on the inhibitory activity were analyzed quantitatively with physicochemical substituent parameters. For 6-substituted (thio)salicylic acids, the activity was shown to vary parabolically with the ‘intramolecular’ steric parameter ( E_s ). In addition, the higher steric dimension of substituents in terms of the STERIMOL width or length parameter lowered the activity. The field-inductive electron-withdrawing property of the 6-substituents in terms of the Swain–Lupton–Hansch F was favorable for the activity of salicylic acid series. In 5-substituted salicylic acids, the activity was increased by electron-donating substituents with smaller size. The relationships between ALS inhibitory and herbicidal activities were also analyzed with some weed species. Both pre- and post-emergence activities against barnyard grass, Echinochloa crus-galli, were linearly related to the ALS inhibitory activity after allowing for the hydrophobic factor that may contribute to the transport processes. Those against two broad-leaved weed species, Polygonum convolvulus and Abutilon theophrasti were linearly related to the in-vitro activity with no significant participation of the hydrophobic factor. © 1998 SCI  相似文献   

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

Chiyozo Takayama  Akira Fujinami 《Pesticide biochemistry and physiology》1979,12(2):163-171

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.  相似文献   

In vivo measurement of house fly temperature,flight muscle potentials,heartbeat and locomotion during insecticide poisoning     

T. Miller  J.M. Kennedy 《Pesticide biochemistry and physiology》1973,3(4):370-383

The average heartbeat rate of female adult Musca domestica was near 250 beats/min in vivo at 23°C. However, standard deviation values ranged from ±35 to ±60 depending on the individual house fly. Heartbeat rates in tethered house flies fluctuated between cessation to over 300 beats/min. The heartbeat rate was temperature dependent with a Q₁₀ of 2.3. Either a bite by the Lynx spider, Peucetia vividans (Hentz), or severing the abdomen from the thorax caused the heartbeat to become extremely steady at near 300 beats/min which gradually decreased over several minutes.Application of lethal doses of Monitor or Lindane to the house fly caused thoracic temperature to increase by at most 3°C in conjunction with increased convulsive activity and increased average heartbeat rate. In late stages of poisoning, the heartbeat was relatively uniform indicating a disruption in cardioregulatory nervous activity. Response of the house fly to carbofuran or its N-thiomethyl analog was similar to that of Monitor and Lindane except in late stages of poisoning where the heartbeat continued to exhibit large variations in average rate.  相似文献   

Quantitative structure-activity studies of benzoylphenylurea larvicides: I. Effect of substituents at aniline moiety against Chilo suppressalis walker     

Yoshiaki Nakagawa  Katsuhiko Kitahara  Takaaki Nishioka  Hajime Iwamura  Toshio Fujita 《Pesticide biochemistry and physiology》1984,21(3):309-325

The larvicidal activity of a series of N-2,6-difluoro- and N-2,6-dichlorobenzoyl-N′-(4-substituted phenyl)ureas against nondiapause larvae of the rice stem borer, Chilo suppressalis Walker, was measured by topical application and oral administration methods under conditions with and without piperonyl butoxide as an inhibitor of oxidative metabolism. The effects of substituents at the anilide moiety on the larvicidal activity were analyzed quantitatively using physicochemical substituent parameters and regression analysis. The results indicate that the oxidative metabolism in the larval body which is favored by electron-donating substituents is significant in determining the activity. The activity, when the metabolic factor is eliminated, is enhanced by electron-with-drawing and hydrophobic substituents and lowered by bulky groups. The inhibitory activity against new cuticle formation of the same series of compounds was also measured using cultured integument of the rice stem borer diapause larva. The comparison of the quantitative analyses between larvicidal and integument-level activities shows that inhibition of cuticular development is the most important factor governing larvicidal activity.  相似文献   

Quantitative structure-activity relationships of herbicidal N′-substituted phenyl-N-methoxy-N-methylureas     

Ichiki Takemoto  Ryo Yoshida  Seizo Sumida  Katsuzo Kamoshita 《Pesticide biochemistry and physiology》1985,23(3):341-348

Relationships between three types of herbicidal activity of N′-substituted phenyl-N-methoxy-N-methylureas and substitution at the benzene ring were analyzed by the Hansch-Fujita method. First, the Hill inhibitory activity was correlated with electronic (σ) as well as hydrophobic (π) substituent constants. The existence of an optimum value of hydrophobicity for substituents was suggested to reach the target site of action. Second, bliaching activity observed for the 3-substituted but not for 4-substituted compounds was correlated with π, σ, and steric substituent constant, E_s. Third, the postemergent herbicidal activity was shown to correlate linearly with the Hill inhibitory activity, pI₅₀, and hydrophobic parameter, π.  相似文献   

Quantitative structure-activity studies of substituted benzyl chrysanthemates: 1. Correlations between symptomatic and neurophysiological activities against American cockroaches     

Shoji Nakagawa  Nobuyuki Okajima  Tetsuo Kitahaba  Keiichiro Nishimura  Toshio Fujita  Minoru Nakajima 《Pesticide biochemistry and physiology》1982,17(3):243-258

A number of substituted benzyl (1R)-trans-chrysanthemates and related compounds were synthesized. Their symptomatic activities in terms of levels which induce convulsions as well as cause death in American cockroaches were determined by injection with and without application of synergists as inhibitors of metabolism. The neuroexcitatory and neuroblocking activities were also determined in terms of minimum effective concentrations to induce repetitive train of impulses and conduction blockage, respectively, to central nerve cords excised from the cockroaches and immersed in Ringer's solution. Correlations between symptomatic and neurophysiological activities were analyzed quantitatively with the aid of molecular hydrophobicity parameter and regression analysis. Each symptomatic activity from which the effect of metabolism is eliminated was found to be analyzable by means of a linear combination of indices for two types of neurophysiological activity when the transport factor is separated by using the hydrophobicity parameter. A closer correlation was found between neuroblocking activity and the “convulsive” effect than between neuroexcitatory activity and the “convulsive” effect, whereas both neurophysiological effects operate together on the cockroaches resulting in paralysis and death.  相似文献   

In vitro inhibition of acetylcholinesterase by O,O-dimethyl S-aryl phosphorothioates     

An-horng Lee  Robert L. Metcalf 《Pesticide biochemistry and physiology》1973,2(4):408-417

In vitro inhibition of house cricket head, house fly head, and bovine erythrocyte acetylcholinesterase by O,O-dimethyl S-aryl phosphorothioates was studied by Main's kinetic treatment. The potency of the compounds as reflected by the bimolecular reaction constants (k_i) indicated that house fly head acetylcholinesterase was the most sensitive to the inhibition followed by house cricket head and bovine erythrocyte acetylcholinesterase. There are no linear relationships between the phosphorylation rate constants and the total binding energies for the inhibition of three enzymes by this series of compounds, suggesting that the initial binding and the phosphorylation rate are not related. The structure and activity relationships were analyzed by multiple regression analyses with the use of Hammett's sigma, alkaline hydrolysis rates of the compounds, and p_i constants. The hydrophobic bonding of the compound on the enzyme surface as reflected by the p_i constant played a significant role in the determination of the potency of the inhibition of house cricket head and house fly head acetylcholinesterase by those compounds. However, the alkaline hydrolysis rates of the compounds, or the Hammett's sigma values seems to play a more important role in the determination of the inhibition of bovine erythrocyte acetylcholinesterase. Moderate insecticidal activity toward house crickets, house flies, and mosquito larvae were found.  相似文献   

The role of tyrosinase in the inactivation of house fly microsomal mixed-function oxidases     

Daune L. Crankshaw  Matthew Zabik  Steven D. Aust 《Pesticide biochemistry and physiology》1977,7(6):564-572

The low mixed-function oxidase activity of house fly microsomes has been associated with low cytochrome P-450 content and NADPH-cytochrome c reductase activity. The microsomal cytochrome P-450 content and NADPH-cytochrome c reductase activity could be decreased by the addition of catechol and increased by the addition of cyanide to the homogenates. Similar results were obtained with rat liver microsomes treated with tyrosinase and catechol. During the inactivation of rat liver microsomal enzymes by tyrosinase and catechol, crosslinking of microsomal proteins occurred. These results suggest that the instability of house fly microsomal mixed-function oxidase may be due in part to the action of contaminating tyrosinase on endogenous substrates.  相似文献   

Quantitative structure—activity relationships of light-dependent herbicidal 4-pyridone-3-carboxanilides I. Effect of benzene ring substituents at the anilide moiety     

Hirokazu Osabe  Yasuo Morishima  Yukihisa Goto  Kazuhisa Masamoto  Yoshiaki Nakagawa  Toshio Fujita 《Pest management science》1992,34(1):17-25

A number of substituted 4-pyridone-3-carboxanilide derivatives show various degrees of light-dependent herbicidal activity. The effects of substituents at the anilide moiety on the activity against Echinochloa oryzicola were analysed quantitatively with physicochemical substituent parameters. The activity was shown to vary parabolically with total hydrophobicity (Σπ) of the anilide ring substituents as well as with the steric parameter (E_s) of the ortho-substituents. The E_s parameter for only the bulkier ortho-substituent, with the more negative value, but not for the two, was significant. The effect of substituents at the 1-position was expressible by indicator variables assigned to each 1-substituted series, the physicochemical rationalization being left for future analyses.  相似文献   

Quantitative structure–fungicidal activity relationships of N-(4-difluoromethoxybenzyl)­pyrimidin-4-amines against wheat and barley fungi     

Yoshinori Yamanaka  Masaru Moritomo  Katsutoshi Fujii  Toshinobu Tanaka  Yasuhisa Fukuda  Keiichiro Nishimura 《Pest management science》1999,55(9):896-902

A set of N-(4-difluoromethoxybenzyl)pyrimidinamines with various substituents at the 4- and 5-positions of the pyrimidine ring and at the benzyl position were prepared, and their fungicidal activities against wheat brown rust, Puccinia recondita, and barley powdery mildew, Erisiphe graminis, were measured. Variations in each of these activities were quantitatively analysed by the use of physicochemical substituent parameters and a regression analysis. Each of these activities was parabolically correlated with the steric bulkiness of the pyrimidine substituents and with the bulkiness or the hydrophobicity of the benzylic substituents. © 1999 Society of Chemical Industry  相似文献   

Steric,electronic, and polar parameters that affect the toxic actions of O-alkyl,O-phenyl phosphonothionate insecticides     

Robert L. Metcalf  Robert A. Metcalf 《Pesticide biochemistry and physiology》1984,22(2):169-177

The toxic action of a series of O-alkyl, O-substituted-phenyl alkyl- and aryl-phosphonates and phosphonothionates have been evaluated by correlating the linear free energy parameters for steric (E_s), electronic (σ), and polar ($\text{σ}{}^1$) effects with topical LD₅₀ to the house fly and oral LD₅₀ to the white mouse. In molecules free from major steric interactions with the reactive P atom, variations in these linear free energy parameters account for >90% of the variations in the LD₅₀ values, and the degree of correlation with LD₅₀ is at least as precise as that with the biomolecular rate constants for inhibition of the target-site enzyme acetylcholinesterase. The value of correlations of linear free energy parameters with LD₅₀ in understanding quantitative structure-activity relationships is illustrated.  相似文献