Design, Synthesis And Biological Activity Of 1,2,4-oxadiazole Derivative

Plant-parasitic nematodes are one of the most severely damaged pathogens in agricultural production,causing up to 150 billion yuan of economic losses worldwide each year.Traditional nematocides have high toxicity,poor efficacy,aging varieties,and are prone to serious resistance issues.However,new nematocides face high production costs,poor persistence,and stability,making it difficult to promote them on a large scale.In response to the current situation that there are many types of plant nematode diseases,their harm is extremely serious,and there are few alternative nematocides available,the creation of new,efficient,low toxicity,low residue,and high selection green nematocides remains the key to the prevention and control of nematode diseases.Tioxazafen is a new type,broad-spectrum,internalized seed treatment nematicide newly developed by Monsanto,which exhibits excellent control effects against a variety of nematodes,but its structure is too simple and lacks the necessary flexibility.Based on this,in this paper,using Tioxazafen as a lead compound,three series of 1,2,4-oxadiazole derivatives were designed and synthesized by introducing nematicidal active amides,chalcones,and haloalkyl pharmacophores into the parent body of 1,2,4-oxadiazole,and their nematicidal activities against Bursapherenchus xylophilus,Aphelenchoides besseiyi,and Ditylenchus dipaci were evaluated,a compound E10 with excellent activity against B.xylophilus was selected,and the preliminary mechanism of action of E10 was discussed.The main research contents are as follows:（1）Three series of 102 1,2,4-oxadiazole derivatives were designed and synthesized,and characterized by ¹H NMR,¹³C NMR,and HRMS.（2）The nematicidal activity of all derivatives was tested using the contact killing method.The results showed that compounds containing haloalkyl groups showed strong nematicidal activity against three nematodes,and compounds E6,E7,and E10showed the best nematicidal activity against A.besseyi,D.dipsaci,and B.xylophilus,with LC₅₀ values of 3.8,2.7,and 2.4μg/m L,respectively,better than fosthiazate（388.5,333.3 and 436.9μg/m L）,avermectin（56.8,285.4 and 335.5μg/m L）and Tioxazafen（>300,142.9 and>300μg/m L）.（3）Combining transcriptome,molecular docking,enzyme activity,and physiological and biochemical indicators to comprehensively reveal the preliminary mechanism of action of compound E10,it was found that the key site of action of compound E10 was acetylcholine receptor,thereby inhibiting AChE activity and causing abnormal neural signal transmission in nematodes.