Design, synthesis, and insecticidal activity evaluation of piperine-phenylene diamine derivatives

Based on the structure of the natural active molecule piperine, a series of novel piperidine-phenylenediamine derivatives were designed and synthesized using a molecular hybridization strategy. The antifeedant activity of all of the compounds against Spodoptera exigua and their cytotoxicity toward Sf9 insect cells were evaluated. The results showed that most of the derivatives exhibited good antifeedant activity, which correlated with their structures. Among them, compound D5 showed the strongest antifeedant activity (EC₅₀=0.184 mg/mL). In the cytotoxicity study, compounds D15 and J1 showed particularly potent antiproliferative effects, with IC₅₀ values of 4.137 µM and 3.726 µM, respectively. Mechanistic studies revealed that both compounds inhibit proliferation by inducing apoptosis and arresting the cell cycle, as evidenced by cell morphology observation, fluorescence staining, and flow cytometry analysis. In summary, the present study provides potential candidates for the development of new environmentally friendly insecticides based on the combination principle.