Application of hydrazide compounds containing dihydrazide structure in prevention and control of golden apple snail
Patent Information
- Application Number
- CN202610689705.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-05-19
- Publication Date
- 2026-09-18
AI Technical Summary
[0004]本发明的目的在于提供含双酰肼结构的酰肼类化合物在防控福寿螺中的新用途，以解决现有化学杀螺剂对非靶标生物毒性高、易产生抗药性等不足，进一步丰富福寿螺防控活性化合物库，为福寿螺绿色防控提供新的解决方案
本发明以福寿螺漆酶为靶标，发现甲氧虫酰肼和环虫酰肼对福寿螺具有显著杀灭活性。室内浸杀试验表明，两种化合物处理福寿螺24h、48h和72h后，校正死亡率分别达到20.00%、55.56%、100.00%和22.00%、63.00%、100.00%，72h的LC50值分别为8.7600mg/L和8.9300mg/L，杀灭效果突出。与已知的漆酶抑制剂白藜芦醇相比，本发明的化合物活性显著更高。白藜芦醇在处理24h、48h和72h后，LC50值分别为132.8934mg/L、58.3273mg/L和38.3538mg/L，而甲氧虫酰肼和环虫酰肼各时间点的LC50值均显著更低，表明其具有更高的靶向活性和杀螺效果。本发明的化合物对脊椎动物低毒，环境安全性好。甲氧虫酰肼和环虫酰肼本身为昆虫生长调节剂类农药，对非靶标节肢动物影响小、对哺乳动物毒性低，符合绿色农药的发展方向。田间试验证实，采用1wt%和3wt%的颗粒剂均匀撒施于水稻田水体中，14d后甲氧虫酰肼颗粒剂对福寿螺的平均防治效果分别达91%和95%，环虫酰肼颗粒剂分别达87%和92%，田间防治效果良好，应用前景广阔。本发明所筛选的化合物为甲氧虫酰肼和环虫酰肼，结构明确，性能稳定，原料易于获取，制剂工艺成熟，有利于进行产业化开发和推广，对于保障水稻等水生作物免受福寿螺危害、减少产量损失具有重要意义。
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of biocidal technology and relates to the application of acylhydrazine compounds containing a diacylhydrazine structure in the control of golden apple snails. Background Technology
[0002] Golden apple snail ( Pomacea canaliculata The golden apple snail (Pomacea canaliculata) severely damages the production of crops such as rice and aquatic vegetables, and disrupts aquatic ecosystems. Furthermore, as an intermediate host for parasites such as Angiostrongylus cantonensis, it poses a potential threat to public health and safety for humans and other mammals. Currently, the control of golden apple snails mainly relies on chemical molluscicides, such as metaldehyde, molluscicides, and their compound formulations. However, the long-term use of traditional chemical molluscicides has revealed several prominent problems: firstly, they are highly toxic to non-target organisms such as fish, frogs, and crustaceans, posing a serious threat to aquatic ecological security; secondly, the long-term repeated application of similar agents has led to drug resistance in some snail populations, resulting in decreased field control efficacy. Therefore, the development of green molluscicides with novel mechanisms of action and good environmental compatibility has become an urgent need in the field of agricultural pest control.
[0003] Target discovery is the core foundation for the creation of novel pesticides. Laccase (EC 1.10.3.2) belongs to the polycopper oxidase family. In mollusks, laccase and phenol oxidase activities have been shown to participate in the innate immune system and play key roles in physiological processes such as eggshell tanning, melanin synthesis, and exogenous substance metabolism. Inhibiting or interfering with laccase activity can affect key processes such as immune defense and eggshell formation, thereby achieving the purpose of killing or eliminating pests. Due to the multiple key functions of laccase in the physiological metabolism of mollusks and the well-defined small molecule binding pocket of its catalytic active site, it has been regarded as a potential molecular target for agricultural pest control. Currently, research on laccase inhibitors has made significant progress mainly in the fields of plant pathogenic fungi and insects. The screening and development of specific drugs targeting golden apple snail laccase is still in its infancy, which has important theoretical exploration significance and practical application value. Summary of the Invention
[0004] The purpose of this invention is to provide a new application of hydrazide compounds containing a dihydrazide structure in the control of golden apple snails, in order to address the shortcomings of existing chemical molluscicides, such as high toxicity to non-target organisms and easy development of drug resistance, further enrich the library of active compounds for the control of golden apple snails, and provide a new solution for the green control of golden apple snails.
[0005] To achieve the above objectives, the present invention provides the following technical solution:
[0006] On one hand, the present invention relates to the application of acylhydrazine compounds containing a diacylhydrazine structure in the control of golden apple snails, wherein the acylhydrazine compounds are methoxyfenozide and / or cyclofenozide.
[0007] The structure of methoxyfenozide is as follows: ; The structure of cyclophosphamide is as follows: .
[0008] Furthermore, in the applications provided by this invention, methoxyfenozide and / or cyclotetracycline are used as active ingredients to prepare suspensions or granules.
[0009] Furthermore, in the application provided by the present invention, the concentration of the active ingredient in the suspension is not less than 4 mg / L.
[0010] Furthermore, in the application provided by the present invention, the concentration of the active ingredient in the granules is not less than 1 wt%.
[0011] On the other hand, the present invention relates to a method for preparing a pharmacokinetic agent for controlling golden apple snails, comprising: using methoxyfenozide and / or cyclotetracycline as the active ingredients of the pharmacokinetic agent for controlling golden apple snails.
[0012] Furthermore, in the preparation method of the golden apple snail control agent provided by the present invention, the dosage form of the golden apple snail control agent is a suspension or granules.
[0013] Furthermore, in the preparation method of the golden apple snail control agent provided by the present invention, the dosage form of the golden apple snail control agent is a suspension, and the concentration of the active ingredient in the suspension is not less than 4 mg / L.
[0014] Furthermore, in the preparation method of the golden apple snail control agent provided by the present invention, the dosage form of the golden apple snail control agent is granules, and the concentration of the active ingredient in the granules is not less than 1 wt%.
[0015] On the other hand, the present invention relates to a method for controlling golden apple snails, comprising: subjecting a hydrazide compound containing a dihydrazide structure and / or a drug having a hydrazide compound containing a dihydrazide structure as an active ingredient to golden apple snails and / or their habitats; Acylhydrazide compounds include methoxyfenozide and / or cyclofenozide.
[0016] Furthermore, in the method for controlling golden apple snails provided by the present invention, the dosage form of the drug is a suspension or granules.
[0017] Compared with the prior art, the technical solution provided by the present invention has at least the following beneficial effects or advantages: This invention targets the laccase of *Pomacea canaliculata* and discovers that methoxyfenozide and cyclotetracycline have significant killing activity against *Pomacea canaliculata*. Indoor immersion tests show that after treatment with the two compounds for 24h, 48h, and 72h, the corrected mortality rates of *Pomacea canaliculata* reached 20.00%, 55.56%, and 100.00%, and 22.00%, 63.00%, and 100.00%, respectively. The LC50 at 72h was [not specified in the original text]. 50 The concentrations were 8.7600 mg / L and 8.9300 mg / L, respectively, demonstrating a significant killing effect. Compared with the known laccase inhibitor resveratrol, the compounds of this invention exhibit significantly higher activity. After treatment with resveratrol for 24 h, 48 h, and 72 h, the LC50 values were [not specified in the original text]. 50 The values were 132.8934 mg / L, 58.3273 mg / L, and 38.3538 mg / L, respectively, while the LC values of methoxyfenozide and cyclotetracycline at each time point were... 50 The values were significantly lower, indicating higher targeting activity and molluscicidal effect. The compounds of this invention have low toxicity to vertebrates and good environmental safety. Methoxyfenozide and cyclofenozide are insect growth regulators, with minimal impact on non-target arthropods and low toxicity to mammals, aligning with the development direction of green pesticides. Field trials confirmed that when 1wt% and 3wt% granules were evenly applied to paddy field water, after 14 days, the average control efficacy of methoxyfenozide granules against golden apple snails reached 91% and 95%, respectively, while that of cyclofenozide granules reached 87% and 92%, respectively, demonstrating good field control effects and broad application prospects. The compounds screened in this invention are methoxyfenozide and cyclofenozide, with well-defined structures, stable performance, readily available raw materials, and mature formulation processes, facilitating industrial development and promotion. This is of great significance for protecting rice and other aquatic crops from golden apple snail damage and reducing yield losses. Detailed Implementation
[0018] The technical solution of the present invention will be described below with reference to embodiments. However, the present invention is not limited to the following embodiments. Unless otherwise specified, the experimental and detection methods described in each embodiment are conventional methods; the reagents and materials described are commercially available unless otherwise specified. Unless otherwise specified, all percentages in the following embodiments refer to mass percentages. Unless otherwise specified, all proportions in the following embodiments refer to mass ratios.
[0019] In the following examples, both methoxyfenozide and cyclotetracycline were purchased from MCE and had a purity of 98%.
[0020] Example 1 This embodiment demonstrates the activity of methoxyfenozide and cyclofenozide in killing golden apple snails.
[0021] The tested golden apple snails were artificially raised by the pollution-free pesticide research laboratory of Sichuan Agricultural University, and individuals with a shell diameter of 5±3 mm were selected for the experiment.
[0022] Using laccase from *Pomacea canaliculata* as the target, two acylhydrazine compounds containing a diacylhydrazine structure, namely methoxyfenozide and cyclotetracycline, were screened to exhibit activity against *Pomacea canaliculata*. The toxic effects of these two diacylhydrazine compounds on *Pomacea canaliculata* were verified by determining the immersion method under different treatment time conditions. The specific method is as follows: Methoxyfenozide and cyclotetracycline were weighed and prepared into 5 mL suspensions with a concentration of 1 g / L. The suspensions contained 5 mg of the compound, 2% dimethyl sulfoxide (DMSO) by volume, 1% Tween 80 by volume, and water to a final volume of 100%. The suspensions were diluted to 5 mg / L and added to each well of a 12-well plate (5 mL per well). Five golden apple snails were placed in each well. Water was used as a blank control instead of the diluent. All other treatment steps were the same. Each treatment was repeated three times. The plates were placed in an incubator at 25°C and 80% humidity. The well openings were sealed with gauze to prevent escape. Mortality was assessed at 24 h, 48 h, and 72 h, and the corrected mortality rate was calculated.
[0023] Corrected mortality rate = [(treatment group mortality rate - control group mortality rate) / (1 - control group mortality rate)] × 100%.
[0024] Table 1 shows the killing effect of two acylhydrazine compounds containing diacylhydrazine structures on golden apple snails at different time points, and Table 2 shows the killing effect of cyclohexane on golden apple snails.
[0025] Table 1: Corrected mortality rate of Pomacea canaliculata treated with methoxyfenozide
[0026] Table 2: Corrected mortality rate of golden apple snails treated with cyclophosphamide
[0027] As shown in Tables 1 and 2, under 25℃ conditions, methoxyfenozide achieved a kill rate of 20%, 60%, and 100% on the tested golden apple snails after immersion treatment for 24, 48, and 72 hours, respectively, with corrected mortality rates of 20.00%, 55.56%, and 100.00%. Similarly, cyclotetracycline achieved a kill rate of 22%, 63%, and 100% on the tested golden apple snails after immersion treatment for 24, 48, and 72 hours, respectively, with corrected mortality rates of 22.00%, 63.00%, and 100.00%. This indicates that both methoxyfenozide and cyclotetracycline have significant killing effects on golden apple snails, and the killing effects of treatments for 48 and 72 hours are significantly better than those for treatments for 24 hours.
[0028] Example 2 This embodiment describes a comparison of the effects of methoxyfenozide, cyclofenozide, and resveratrol (an existing laccase inhibitor) on killing golden apple snails.
[0029] The tested golden apple snail was the same as in Example 1. The experimental method employed was an immersion method to determine the killing effects of two acylhydrazine compounds containing a dihydrazide structure and resveratrol on the golden apple snail at different concentrations. The specific procedure is as follows: Methoxyfenozide, cyclofenozide, and resveratrol were each prepared into 5 mL suspensions with a concentration of 1 g / L. The suspensions contained 5 mg of each compound, 2% dimethyl sulfoxide (DMSO) by volume, 1% Tween 80 by volume, and water to a final volume of 100%. These were then diluted to concentrations of 4 mg / L, 6 mg / L, 8 mg / L, 10 mg / L, and 12 mg / L, respectively. 5 mL of each dilution was added to each well of a 12-well plate. Five golden apple snails were placed in each well of the plate. Water was used as a blank control instead of the dilution. All other treatments were performed in the same manner, with each treatment repeated three times. The plates were placed in an incubator at 25°C and 80% humidity. The well openings were sealed with gauze to prevent escape. Mortality was assessed at 24 h, 48 h, and 72 h. A toxicity regression equation was established, and the LC50 was calculated. 50 value.
[0030] The toxicity regression equations and LC-1 of two acylhydrazide compounds containing a dihydrazide structure and resveratrol against golden apple snails. 50 The values are shown in Table 3.
[0031] Table 3. Toxicity regression equations and LC-12 values for two acylhydrazine compounds containing a dihydrazide structure. 50 value
[0032] Table 3 shows that after treatment for 24h, 48h, and 72h, the LC50 of resveratrol on the tested golden apple snail was... 50 The LC50 values for methoxyfenozide against the tested golden apple snail were 132.8934 mg / L, 58.3273 mg / L, and 38.3538 mg / L, respectively. 50 The LC50 values for cyclophosphamide against the tested golden apple snail were 9.1233 mg / L, 15.4121 mg / L, and 8.7600 mg / L, respectively. 50 The values were 12.3315 mg / L, 13.6521 mg / L, and 8.9300 mg / L, respectively, all lower than resveratrol. Furthermore, the LC values of the two acylhydrazine compounds containing dihydrazide structures after treatment for 48 h and 72 h were... 50 The value was significantly lower than that of LC after 24 hours of treatment. 50The results indicate that the two hydrazide compounds containing dihydrazide structures have higher activity and better killing effect on golden apple snails compared with resveratrol, and the killing effect is significant after 48 hours of treatment.
[0033] Example 3 This example describes the field experiment results of methoxyfenozide and cyclofenozide in killing golden apple snails.
[0034] Methoxyfenozide and cyclofenozide were prepared into granules. The granule composition is as follows: 1-6 wt% of acylhydrazine compounds containing a diacylhydrazine structure, 1 wt% of rapeseed oil, 2 wt% of sodium carboxymethyl cellulose (binder), 5 wt% of white sugar, 5% of cream flavoring, and corn flour to make up to 100 wt%. The granules were prepared and provided by the Pollution-Free Pesticide Research Laboratory of Sichuan Agricultural University.
[0035] The experimental plots were selected with clay soil of moderate fertility, and all cultivation conditions were consistent. Each plot was 5m² in size. 2 One hundred clumps of seedlings (5 seedlings per clump) were transplanted to each plot, and the clumps were isolated with plastic film to maintain a water depth of 5 ± 2 cm. Seven days after transplanting, 100 golden apple snails of uniform size were artificially released into each plot. Granules containing two different hydrazide compounds (1 wt%, 3 wt%, and 6 wt%) were evenly applied to the water. The control group received no treatment. Each treatment was replicated three times. Mortality of the golden apple snails in the plots was investigated at 1, 3, 7, and 14 days after application, and the corrected mortality rate was calculated.
[0036] Corrected mortality rate = [(treatment group mortality rate - control group mortality rate) / (1 - control group mortality rate)] × 100%.
[0037] Table 4: Field control efficacy of methoxyfenozide granules (%)
[0038] Table 5: Field control efficacy of cyclophosphamide granules (%)
[0039] Tables 4 and 5 show that 1 wt% methoxyfenozide granules and 3 wt% methoxyfenozide-containing granules showed good field control efficacy against *Pomacea canaliculata*, with average control efficiencies of 91% and 95% respectively after 14 days. Similarly, 1 wt% cyclone dichlorvos granules and 3 wt% cyclone dichlorvos-containing granules also showed good field control efficacy against *Pomacea canaliculata*, with average control efficiencies of 87% and 92% respectively after 14 days. However, the mortality rate of *Pomacea canaliculata* decreased when using 6 wt% methoxyfenozide and cyclone dichlorvos granules, mainly due to the snails refusing to feed.
[0040] In summary, this invention targets the laccase of *Pomacea canaliculata* and screens for two acylhydrazine compounds with a dihydrazide structure that exhibit activity against *Pomacea canaliculata*: methoxyfenozide and cyclofenozide. These two acylhydrazine compounds, when prepared as suspensions or granules, both demonstrate excellent killing effects against *Pomacea canaliculata*. Compared to the existing laccase inhibitor resveratrol, they exhibit higher activity, better selectivity, and lower toxicity to vertebrates, showing great application potential.
[0041] The embodiments described above are only some, not all, of the embodiments of the present invention. The detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely to illustrate preferred embodiments. All other embodiments obtained by those skilled in the art through related deductions and substitutions based on the inventive concept, without inventive effort, are within the scope of protection of the present invention.
Claims
1. The application of acylhydrazine compounds containing a dihydrazide structure in the control of golden apple snails, characterized in that, The acylhydrazide compounds are methoxyfenozide and / or cyclofenozide.
2. The application of the acylhydrazine compound containing a diacylhydrazine structure according to claim 1 in the control of golden apple snails, characterized in that, Methoxyfenozide and / or cyclofenozide are used as active ingredients to formulate suspensions or granules.
3. The application of the acylhydrazine compound containing a diacylhydrazine structure according to claim 2 in the control of golden apple snails, characterized in that, The concentration of the active ingredient in the suspension is not less than 4 mg / L.
4. The application of the acylhydrazine compound containing a diacylhydrazine structure according to claim 2 in the control of golden apple snails, characterized in that, The concentration of the active ingredient in the granules is not less than 1 wt%.
5. A method for preparing a pesticide for controlling golden apple snails, characterized in that, include: Methoxyfenozide and / or cyclofenozide are used as the active ingredients in the golden apple snail control agent.
6. The method for preparing the golden apple snail control agent according to claim 5, characterized in that, The dosage form of the golden apple snail control agent is a suspension or granules.
7. The method for preparing the golden apple snail control agent according to claim 5, characterized in that, The golden apple snail control agent is in the form of a suspension, and the concentration of the active ingredient in the suspension is not less than 4 mg / L.
8. The method for preparing the golden apple snail control agent according to claim 5, characterized in that, The golden apple snail control agent is in granule form, and the concentration of the active ingredient in the granule is not less than 1 wt%.
9. A method for controlling golden apple snails, characterized in that, This enables acylhydrazine compounds containing a diacylhydrazine structure and / or drugs with said diacylhydrazine compounds as active ingredients to act on golden apple snails and / or their habitats; The acylhydrazide compounds are methoxyfenozide and / or cyclofenozide.
10. The method for controlling golden apple snails according to claim 9, characterized in that, The drug is in the form of a suspension or granules.