Design, Synthesis, and Bioactivity of 5-Chloro-Indane Derivatives Containing Guanidine

Sodium channels play a crucial role in insect neuronal cell activity, and inhibitors targeting insect sodium channels are considered a promising insecticidal strategy. In this study, we designed and synthesized a series of 5-chloro-Indane derivatives containing guanidine targeting insect sodium channels, among which compounds <b>9f</b>, <b>9n</b>, and <b>9o</b> showed good insecticidal activity against the <i>Plutella xylostella</i>, <i>Spodoptera exigua</i>, <i>Spodoptera litura</i>, and <i>Mythimnaseparata walker</i>. The inhibition rate of sodium current of compounds <b>9f</b>, <b>9n</b>, and <b>9o</b> with better insecticidal activity was determined by electrophysiological experiments, and the mechanism of action of compound <b>9f</b> affecting the growth and development of insects was further analyzed by combining with transcriptomics. In addition, the binding modes and interactions between the compounds and sodium channels were explored by molecular docking and molecular dynamics simulations. This study provides a promising strategy for the development of novel insect sodium channel inhibitors as potential pest control agents.