Design, Synthesis, and Bioactivity of Spiro Derivatives Containing a Pyridine Moiety

We designed and synthesized a series of pyridine spiro derivatives and evaluated their insecticidal and antiviral activities. Some compounds exhibited good insecticidal and antiviral activities. Notably, the E series of compounds displayed good insecticidal activity against Tetranychus urticae. Compounds E20 (EC₅₀ = 63.68 mg/L) and F4 (EC₅₀ = 47.81 mg/L) exhibited inactivation activities against the tobacco mosaic virus (TMV), which were similar to that of Ningnanmycin (EC₅₀ = 58.01 mg/L). Molecular docking showed that compounds E20 and F4 exhibited satisfactory affinities for the TMV coat protein (TMV-CP), with binding energies (-6.7 and -6.4 kcal/mol, respectively) slightly lower than that of Ningnanmycin (-6.3 kcal/mol). Further, molecular dynamics analysis revealed that compounds E20 and F4 exhibited better binding stability values than Ningnanmycin. Microscale thermophoresis showed that compounds E20 (K_d = 0.053 ± 0.016 μM) and F4 (K_d = 0.045 ± 0.022 μM) bound more strongly to TMV-CP than Ningnanmycin (K_d = 0.10 ± 0.029 μM). The results of transmission electron microscopy showed that these two compounds hindered the self-assembly and growth of TMV. In summary, we showed that these pyridine spiro derivatives could be used as a basis for the research and development of novel pesticides.