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 (Kd = 0.053 +/- 0.016 mu M) and F4 (Kd = 0.045 +/- 0.022 mu M) bound more strongly to TMV-CP than Ningnanmycin (Kd = 0.10 +/- 0.029 mu M). 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.

Automated summary

In this study, we designed and synthesized a series of pyridine spiro derivatives and evaluated their insecticidal and antiviral activities. Some compounds showed good insecticidal and antiviral activities, especially the E series compounds against Tetranychus urticae. Molecular docking, molecular dynamics, and microscale thermophoresis experiments revealed that compounds E20 and F4 exhibited satisfactory binding affinities for the tobacco mosaic virus coat protein (TMV-CP) and showed better binding stability values than Ningnanmycin. The results also indicated that these compounds hindered the self-assembly and growth of TMV.