反抗性新煙堿殺蟲劑的開發

徐曉勇

摘 要：作用于煙堿型乙酰膽堿受體（nAChRs）的新煙堿類殺蟲劑自問世以來由于其活性高，殺蟲譜廣，對哺乳動物和水生動物毒性低，且有良好的內吸性及適當的田間穩定性而成為農藥創制的重要熱點領域。隨著新煙堿類殺蟲劑品種的大量頻繁使用，已經產生了嚴重抗性，2005年稻飛虱對吡蟲啉的抗性高達400倍以上，此外，由于頻繁持續的使用，也對環境產生一定的負面影響，如，在歐洲和日本都相繼發現吡蟲啉對蜜蜂種群的影響，最高減少40%的蜜蜂數量，嚴重影響了作物花粉的傳播。因此，從新的作用模型出發，針對業已出現的抗性問題和蜜蜂毒性，以提高生物選擇性為切入點，開展靶向性的分子設計與合成，這對我國具有自主知識產權的新農藥創制和農業害蟲防治都具有重要意義。主要研究內容：（1）系統研究稻飛虱、煙粉虱等重大農業害蟲對吡蟲啉等新煙堿殺蟲劑的抗性機制和基于分子靶標的作用模型；（2）以超高活性的順硝烯化合物為基礎，研究高活性的先導化合物生物合理性分子設計、先導結構多樣性衍生與優化，創制順硝烯反抗性新煙堿殺蟲劑；（3）研究基于抗性機制的分子生物學和分子毒理學，建立與完善基于分子靶標的反抗性殺蟲劑創制體系。預期目標：通過超高活性的先導化合物生物合理性分子設計、先導結構多樣性衍生與優化研究，強化我國在順硝烯反抗性新煙堿殺蟲劑創制領域的優勢。在活性化合物的基礎上，開展基于抗性機制的分子生物學和分子毒理學研究，建立與完善基于分子靶標的反抗性機制殺蟲劑創制體系。申請國際PCT專利，并進入指定國，進行高活性化合物的中試工藝研究，完成擴大殺蟲譜試驗和小區試驗測試高活性化合物的急性經皮、經口、急性吸入、Ames試驗、蜜蜂毒性等數據，為申請農藥登記證做好前期工作。

關鍵詞：反抗性 新煙堿 順式構型

Abstract：Neonicotinoids acting on nAChRs have become the important hot-point research area because of its high bioactivities， broad spectrum， low toxicity to mammal and aquatic organisms， good systemic and suitable stability since they came into the market. With the using of large amount of neonicotinoids， the resistance is becoming very serious. The resistance ratio to imidacloprid aganist brown planthopper reached to 400 folds in 2005. In addition， frequent and continuous use result in negitive effect to the environment， for example， it was found in succession that imidacloprid influented the bee populations in Europe and Japan， the amount of bee decrease 40%， which affected seriously the spead of crop plllen. Therefore， based no the new model of action， targeting on the emerging resistance and bee toxicity， to improve the biological selectivity as the breakthrough point， we begin to target-orientation molecular design and synthesis， which is significant for the research and development of new pesiticde with independent intellectual property rights and the agricultural pest control. Main research content：（1）systemic research the resisitance mechanism and the model of action based on the molecular target of imidacloprid to planthopper and besimia tabaci etc. important agricultural pests；（2）Study the biological rational design of leading compounds with high activities， derivative and modification of lead structures based on the super high bioactivity of cis-configuration nitro methelene compounds and develop cis-configuration anti-resictance insecticide；（3）Study the molecular biology and toxicology based on the resistance mechanism and build and improve the research and development system of anti-resistance insecticides. Target： Through the study on the biological rational design of leading compounds with super high activities， derivative and modification of lead structures， the advantage of cis-configuration nitro methelene anti-resictance insecticide in our country is strengthened further. Based on the strucuture of the compound with activities， the researches on the molecular biology and toxicology based on the resistance mechanism are carried out and build and improve the research and development system of anti-resistance insecticides. To apply the PCT patent and come into the foreign countries， study the pilot process of the compound with hign activities， finish the experiments on broad spectrum and field trial， detemination the data of acute Acute percutaneous， acute through the mouth， acute inhalation， Ames test， bee toxicity， prepare the early stage work for the application of pesticide registration certificate.

Key Words：Anti-resistance；Neonicotinoids；Cis-configuration

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