Use of an amide compound as a pesticide synergist

Abstract

The application belongs to the technical field of pesticide synergists, and discloses a use of an amide compound as a pesticide synergist. The application takes CYP6AE48 of Spodoptera litura as a main target, adopts a method combining computer-aided drug design technology and biological effect screening, and screens an amide compound, which is N-{5-[2-(2-{3-[2-(2-methylphenoxy)ethoxy]benzyl}hydrazino)-2-oxoethyl]-1,3,4-thiadiazol-2-yl}benzamide. It is known through experiments that the compound has a good inhibitory effect on CYP6AE48 of Spodoptera litura, can prevent degradation of lambda-cyhalothrin and chlorantraniliprole, and can play a synergistic effect as a pesticide synergist in pest control.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of pest control, and particularly relates to a use of an amide compound as a pesticide synergist. BACKGROUND

[0002] Spodoptera litura Fabricius belongs to Lepidoptera Noctuidae and is a polyphagous and voracious pest with extremely strong reproductive capacity, which can reproduce multiple generations in one year, generations overlap, and can harm 109 families and 389 species of host plants, and is one of the main pests of vegetables, cotton, grains and oils, and various greening plants.

[0003] At present, chemical pesticides are mainly used to control pests in the field, which is simple and convenient, can quickly and effectively control the expansion of pest population, and has played a significant effect in pest control. However, due to long-term repeated use of insecticides, Spodoptera litura develops resistance to insecticides very quickly, for example, different levels of resistance to chlorantraniliprole, cypermethrin, abamectin and other insecticides. Studies have shown that the mechanism of insect resistance includes: the penetration rate of insecticides on the cuticle of the insect body is reduced, the detoxification and metabolism of the insect body to insecticides is enhanced, and the sensitivity of the target site is reduced, etc.

[0004] Cytochrome P450 monooxygenase (P450 enzyme for short) belongs to monooxygenase, which can participate in the metabolism and detoxification of exogenous substances (such as insecticides, plant secondary metabolites, etc.), and also participates in the synthesis and metabolism of endogenous substances of insects. Piperonyl butoxide (piperonyl butoxide) is the most widely used P450 enzyme inhibitor, which has been on the market for many years as a pesticide synergist. PBO is a semi-natural compound synthesized from safrole, which can inhibit a variety of P450 enzymes related to biosynthesis reactions, thereby improving the insecticidal activity of a variety of insecticides, but has no obvious effect on P450 enzymes related to detoxification and metabolism. However, many studies have shown that the main reason for the development of resistance and cross-resistance of most pests to insecticides is the enhancement of P450 enzymes related to detoxification and metabolism. Therefore, the development of P450 enzyme inhibitors related to detoxification and metabolism is expected to play a synergistic effect as a pesticide synergist in pest control. SUMMARY

[0005] In order to enrich the types of existing pesticide synergists and further enhance the effect of pest control, the present application takes CYP6AE48 enzyme (a P450 enzyme related to detoxification metabolism) as the main target, adopts the method of computer-aided drug design technology combined with biological effect screening, screens an amide compound, and proves that the compound has the promotion effect on the control effect of lambda-cyhalothrin and chlorantraniliprole. In order to achieve the technical purpose, the present application adopts the following technical scheme.

[0006] Firstly, the present application provides a use of an amide compound as a pesticide synergist, wherein the amide compound is N-{5-[2-(2-{3-[2-(2-methylphenoxy)ethoxy]benzyl}hydrazyl)-2-oxoethyl]-1,3,4-thiadiazol-2-yl}benzamide.

[0007] Further, in the use, the amide compound inhibits the cytochrome p450 enzyme of the C. punctiferalis.

[0008] Further, in the use, the cytochrome p450 enzyme of the C. punctiferalis is CYP6AE48 enzyme.

[0009] Based on the above use, another aspect of the present application provides a method for improving the chemical control effect of C. punctiferalis, which comprises: using the above-mentioned amide compound as a cytochrome p450 enzyme inhibitor of C. punctiferalis to act on C. punctiferalis.

[0010] Further, in the method, the cytochrome p450 enzyme of the C. punctiferalis is CYP6AE48 enzyme.

[0011] Further, in the method, the amide compound is dissolved in dimethyl sulfoxide to prepare a solution with a concentration of 10 g / L, and the solution is used in an amount of 20 μg per head.

[0012] Further, the chemical control comprises: using lambda-cyhalothrin for control and using chlorantraniliprole for control.

[0013] Further specifically, the amide compound improves the effect of lambda-cyhalothrin on C. punctiferalis by 1.9343, 2.4639, 2.2816 times at 24, 48, 72 h; and the amide compound improves the effect of chlorantraniliprole on C. punctiferalis by 1.6438, 1.0128 times at 24 h and 72 h.

[0014] Compared with the prior art, the present application "a use of an amide compound as a pesticide synergist" has the following beneficial effects:

[0015] The present application takes CYP6AE48 enzyme of Spodoptera litura as the main target, adopts the method of combining computer-aided drug design technology with biological effect screening, and screens an amide compound, which is N-{5-[2-(2-{3-[2-(2-methylphenoxy)ethoxy]benzyl}hydrazinyl)-2-oxoethyl]-1,3,4-thiadiazol-2-yl}benzamide. Specifically, the compound makes the effect of lambda-cyhalothrin on Spodoptera litura increase by 1.9343, 2.4639, 2.2816 times at 24, 48, 72 h; the amide compound makes the effect of chlorantraniliprole on Spodoptera litura increase by 1.6438, 1.0128 times at 24 h, 72 h, which indicates that the compound can better inhibit the activity of CYP6AE48 enzyme of Spodoptera litura, so that it cannot normally play the detoxification function on lambda-cyhalothrin and chlorantraniliprole, and further improves the control effect of lambda-cyhalothrin and chlorantraniliprole, and the compound can be used as a pesticide synergist to play a synergistic effect in pest control.

[0016] On the other hand, the existing P450 enzyme inhibitors (such as piperonyl butoxide) mainly inhibit the P450 enzymes related to biosynthesis reactions, while the P450 enzymes related to detoxification metabolism are the main reason for the resistance and cross-resistance of most pests to insecticides, and are more important for pest control. The present application takes the P450 enzyme CYP6AE48 related to detoxification metabolism of Spodoptera litura as the target, and screens a P450 enzyme inhibitor related to detoxification metabolism, which makes up for the technical defects of the relative lack of this kind of enzyme inhibitors, which has important enlightenment and guiding significance for the future research of pesticide synergists. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 The chemical structural formula of the amide compound is shown. DETAILED DESCRIPTION

[0018] The present application will be described below in conjunction with the embodiments, and the technical solutions in the embodiments of the present application are described clearly and completely. Obviously, the described embodiments are only some of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0019] The experimental methods in the following embodiments are all conventional methods, and are carried out according to the techniques or conditions described in the literature in the art or according to the product instructions, unless otherwise specified. The materials, reagents and the like used in the following embodiments can be obtained from commercial channels, unless otherwise specified.

[0020] In the following examples, the amide compound is: N-{5-[2-(2-{3-[2-(2-methylphenoxy)ethoxy]benzyl}hydrazino)-2-oxoethyl]-1,3,4-thiadiazol-2-yl}benzamide (CAS No. 380874-27-1, purity 99%), which is purchased from specs. The chemical structural formula of the compound is shown in Figure 1 .

[0021] Example 1

[0022] This example describes the killing effect of lambda-cyhalothrin alone on Spodoptera litura.

[0023] Test method: lambda-cyhalothrin technical material is weighed, and a 1 g / L stock solution is prepared using acetone as a solvent. Then, the stock solution is diluted to 3, 2, 1.5, 1, and 0.5 mg / L to obtain lambda-cyhalothrin solutions.

[0024] The 3rd instar larvae of Spodoptera litura are used as test insects, and the lambda-cyhalothrin solution is dropped on the prothoracic dorsal plate of each larva using a micro-dropper, with 1 μL per larva. After natural air drying, the larvae are placed in an incubator with a temperature of 27±1°C, a relative humidity of 70%, and a light duration of 12 h. Acetone is used as a control group, and the rest of the steps are the same. Each culture dish contains 20 larvae, and the experiment is repeated three times. The results are observed after 24, 48, and 72 h, respectively. A larva that does not wriggle when touched with a brush is considered dead. The SPSS software is used to calculate the toxicity regression equation, correlation coefficient, and LC 50 .

[0025] Test results: see Table 1. As shown in Table 1, when lambda-cyhalothrin is used alone, the LC 50 values at 24, 48, and 72 h are 2.5695, 2.3338, and 2.0676 mg / L, respectively.

[0026] Table 1. Effect of using lambda-cyhalothrin alone

[0027] Time Virulence equation Correlation coefficient r (95% confidence interval) LC 50 (mg / L) 24h Y = 2.6323X + 3.9211 0.9944 2.5695 48h Y = 2.5278X + 4.0696 0.9838 2.3338 72h Y = 2.8459X + 4.1022 0.9921 2.0676

[0028] Example 2

[0029] This example describes the effect of using the amide compound when lambda-cyhalothrin is used.

[0030] Test method: lambda-cyhalothrin technical material is weighed, and a 1 g / L stock solution is prepared using acetone as a solvent. Then, the stock solution is diluted to 0.5, 1, 1.5, 2, and 3 mg / L to obtain lambda-cyhalothrin solutions. The amide compound is prepared at a concentration of 10 g / L using dimethyl sulfoxide as a solvent.

[0031] The solution of the amide compound was dropped on the prothorax of the 3rd instar larvae of Spodoptera litura by using a micro-dropper, 20 μg per larva, and then dried naturally for 1 h. The solution of lambda-cyhalothrin was dropped on the prothorax of the larvae by using the same method, 1 μl per larva. After the dropping, the larvae were placed in an incubator, the temperature of which was 27±1℃, the relative humidity was 70%, and the light duration was 12 h. The control group was treated with dimethyl sulfoxide instead of the solution of the amide compound, and the rest of the treatment steps were the same. Each culture dish contained 20 larvae, and the experiment was repeated 3 times. The results were observed after 24, 48 and 72 h, respectively. A larva was considered dead if it did not wriggle when touched with a brush. The toxicity regression equation, correlation coefficient and LC 50 values were calculated by using SPSS software, and the synergistic ratio was calculated.

[0032] Synergistic ratio (SR) = LC 50 of lambda-cyhalothrin alone / LC 50 of lambda-cyhalothrin when the amide compound is added.

[0033] Test results: see Table 2.

[0034] Table 2. Effect of lambda-cyhalothrin when the amide compound is added

[0035]

[0036]

[0037] As shown in Table 1 and Table 2, at 24, 48 and 72 h, the LC 50 values of lambda-cyhalothrin when the amide compound is added were significantly lower than the LC 50 values of lambda-cyhalothrin alone, indicating that the CYP6AE48 enzyme of Spodoptera litura was inhibited by the amide compound, and thus could not normally detoxify lambda-cyhalothrin. Therefore, the effect of lambda-cyhalothrin when the amide compound is added is better, which is consistent with the expectation. In addition, at 24, 48 and 72 h, the synergistic ratios were 1.9343, 2.4639 and 2.2816 times, respectively, all of which were greater than 1, indicating that the amide compound has a good effect.

[0038] Example 3

[0039] This example describes the killing effect of chlorantraniliprole alone on Spodoptera litura.

[0040] Test method: chlorantraniliprole technical material was weighed, and a 1 g / L stock solution was prepared by using acetone as a solvent. Then, the stock solution was diluted to 1.2, 1, 0.8, 0.6 and 0.4 mg / L to obtain chlorantraniliprole solutions.

[0041] The 3rd instar larvae of Helicoverpa armigera were used as test insects, and the chlorantraniliprole solution was dropped on the prothoracic dorsal plate of the larvae using a micro-dropper, 1 μL per larva. After natural air drying, the larvae were placed in an incubator, the temperature of which was 27±1°C, the relative humidity was 70%, and the light duration was 12 h. Acetone was used as the control group, and the rest of the treatment steps were the same. Each culture dish contained 20 larvae, and the experiment was repeated 3 times. The results were observed after 24, 48, and 72 h, respectively, and the number of dead insects was recorded. If the larvae did not wriggle when touched with a brush, they were considered dead. The toxicity regression equation, correlation coefficient, and LC 50 .

[0042] The test results are shown in Table 3. According to Table 3, at 24, 48, and 72 h, the LC 50 values of chlorantraniliprole used alone were 1.6794, 0.5241, and 0.4721 mg / L, respectively.

[0043] Table 3. Effect of chlorantraniliprole used alone

[0044]

[0045] Example 4

[0046] This example describes the effect of the amide compound when used with chlorantraniliprole.

[0047] Test method: Chlorantraniliprole technical material was weighed, and a 1 g / L stock solution was prepared using acetone as the solvent. Then, the solution was diluted to 1.2, 1, 0.8, 0.6, and 0.4 mg / L to obtain the chlorantraniliprole solution. Another 10 g / L amide compound solution was prepared using dimethyl sulfoxide as the solvent.

[0048] The 3rd instar larvae of Helicoverpa armigera were used as test insects, and the amide compound solution was dropped on the prothoracic dorsal plate of the larvae using a micro-dropper, 20 μg per larva. After natural air drying for 1 h, the chlorantraniliprole solution was dropped on the prothoracic dorsal plate of the larvae using the same method, 1 μL per larva. After the dropping was completed, the larvae were placed in an incubator, the temperature of which was 27±1°C, the relative humidity was 70%, and the light duration was 12 h. The control group used dimethyl sulfoxide instead of the amide compound solution, and the rest of the treatment steps were the same. Each culture dish contained 20 larvae, and the experiment was repeated 3 times. The results were observed after 24, 48, and 72 h, respectively, and the number of dead insects was recorded. If the larvae did not wriggle when touched with a brush, they were considered dead. The toxicity regression equation, correlation coefficient, and LC 50 were calculated using SPSS software, and the synergistic ratio was calculated.

[0049] Synergistic ratio (SR) = LC 50 of chlorantraniliprole used alone / LC 50 of chlorantraniliprole used with the addition of the amide compound.

[0050] Test results: see Table 4.

[0051] Table 4. Effect of chlorantraniliprole when the amide compound is added

[0052]

[0053] From Table 3 and Table 4, it can be seen that at 24h, 72h, the LC 50 values of chlorantraniliprole when the amide compound is added are lower than the LC 50 values when chlorantraniliprole is used alone, and the LC 50 values at 48h are slightly higher, which may be due to test errors. The synergistic multiples at 24h and 72h are 1.6438 and 1.0128 respectively, indicating that the addition of the amide compound has a certain enhancing effect on the control effect of chlorantraniliprole.

[0054] In summary, the present application takes CYP6AE48 of Spodoptera littoralis as the main target, adopts the method of combining computer-aided drug design technology with biological effect screening, and screens an amide compound, which is N-{5-[2-(2-{3-[2-(2-methylphenoxy)ethoxy]benzyl}hydrazyl)-2-oxoethyl]-1,3,4-thiadiazol-2-yl}benzamide. It is known through tests that the compound has good inhibitory effect on CYP6AE48 of Spodoptera littoralis, prevents the degradation of high-efficiency lambda-cyhalothrin and chlorantraniliprole, and is expected to play a synergistic effect as a pesticide synergist in pest control.

[0055] The above-described embodiments are only some of the embodiments of the present application, not all the embodiments. The detailed description of the embodiments of the present application is not intended to limit the scope of the claimed application, but only represents selected embodiments of the application. All other embodiments obtained by related deduction and replacement of those skilled in the art under the condition of the concept of the present application, without making creative efforts, belong to the scope of protection of the present application.

Claims

1. Use of an amide compound as a pesticide synergist, characterized in that, The amide compound is N-{5-[2-(2-{3-[2-(2-methylphenoxy)ethoxy]benzyl}hydrazino)-2-oxoethyl]-1,3,4-thiadiazol-2-yl}benzamide.

2. Use according to claim 1, characterized in that, The amide compound inhibits the cytochrome p450 enzyme of Spodoptera littoralis.

3. Use according to claim 2, characterized in that, The cytochrome p450 enzyme of Spodoptera littoralis is CYP6AE48 enzyme.

4. A method of enhancing the chemical control of Spodoptera exigua, characterized in that, The method comprises: using the amide compound as an inhibitor of cytochrome p450 enzyme of Spodoptera littoralis to act on Spodoptera littoralis. The amide compound is N-{5-[2-(2-{3-[2-(2-methylphenoxy)ethoxy]benzyl}hydrazino)-2-oxoethyl]-1,3,4-thiadiazol-2-yl}benzamide.

5. The method of claim 4, wherein, The cytochrome p450 enzyme of Spodoptera littoralis is CYP6AE48 enzyme.

6. The method of claim 4, wherein, The amide compound is dissolved in dimethyl sulfoxide to prepare a solution with a concentration of 10 g / L, and the solution is used in an amount of 20 μg per head.

7. The method of claim 4, wherein, The chemical control comprises: using lambda-cyhalothrin for control and using chlorantraniliprole for control.

8. The method of claim 7, wherein, The amide compound improves the control effect of lambda-cyhalothrin on Spodoptera littoralis by 1.9343, 2.4639, 2.2816 times at 24, 48, 72 h.

9. The method of claim 7, wherein, The amide compound improves the control effect of chlorantraniliprole on Spodoptera littoralis by 1.6438, 1.0128 times at 24, 72 h.

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