Synthesis, biological activity, and binding modes of novel guanidino-containing neonicotinoid derivatives

Abstract

In the present study, the guanidine moiety from natural products was introduced into neonicotinoid insecticides, and a series of nicotine derivatives with guanidine functional groups were synthesized. Bioactivity assays reveal that compounds 7a and 7i, despite having significant structural differences, both exhibit notable insecticidal activity. Molecular docking, MD simulations, and aNCI results indicate different binding modes between nAChR and the compounds, with 7a exhibiting predominantly hydrophobic interactions and 7i showing dominance in hydrogen bonding interactions. The analysis concluded that using cyclic structures for structural derivation may be a more efficient strategy for designing inhibitors of nAChR.