Design, Synthesis, Biological Activity Evaluation Of Imidacloprid And Cantharidin Derivatives

In order to find new insecticides of low toxicity and high efficiency, three novel series of N3-substituted imidacloprid derivatives were designed and synthesized, and their structures were identified on the basis of satisfactory analytical and spectral (1H NMR,13C NMR, MS, elemental analysis and X-ray) data. Preliminary bioassays indicated that all of the derivatives exhibited significant insecticidal activities against Aphis craccivora, with LC50 values ranging from 0.00895 to 0.49947 mmol/L, and the insecticidal activities of some of them were comparable to those of the control imidacloprid. Some structural features important for potency were observed, and the binding modes between target compounds and nAChRs were also further explored by molecular docking. We analyzed that what caused the high insecticidal activity of compound 26. The molecular docking analysis indicated that the π-π stacking, hydrogen bond and hydrophobic interactions played important roles for the binding of these derivatives to nAChRs. Based on the conformations generated by molecular docking, a 2D-QSAR model with six selected descriptors was built using Genetic Algorithm-Multiple Linear Regression (GA-MLR) method. The six selected descriptors are T(O..Cl), EEig08x, BELm7, RDF140u, Mor12m, Mor16m. The model is satisfactory with correlation coefficient Rtr2. of 0.9479, cross-validated correlation coefficient Qloo2 of 0.9287, and the external validation coefficient Qext2 of 0.9270. The analysis of the built model showed the molecular size, shape and the ability to form hydrogen bond were important for insecticidal potency. The information obtained in the study will be very helpful for the design of new derivatives with high insecticidal activities.Traditional insecticides have some impact on the entire food chain, insects would gradually have resistance. Therefore, in an attempt to find the biorational pesticides, in order to achieve the purpose of insects prevention and cure each other, a series of novel acylthiourea derivatives of cantharidin were designed, synthesized and preliminarily evaluated for their bioactivities against Tetranychus Cinnabarinus and Brevicoryne brassicae. All the new compounds showed significant acaricidal activities against Tetranychus Cinnabarinus with LC50 values ranging from 0.695 to 2.934 mmol/L. In particular, compounds 6i and 6g exhibited the greatest acaricidal activity against Tetranychus Cinnabarinus in all derivatives we prepared. Moreover, all of these compounds displayed better acaricidal activities against Tetranychus Cinnabarinus than insecticidal activities against Brevicoryne brassicae. Based on the observed bioactivities, the structure-activity relationship (SAR) of these analogs was also discussed. The present work indicated that some cantharidin derivatives can be used as potential lead compounds for developing novel insecticides and acaricides.