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

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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 9f, 9n, and 9o showed good insecticidal activity against the Plutella xylostella, Spodoptera exigua, Spodoptera litura, and Mythimnaseparata walker . The inhibition rate of sodium current of compounds 9f, 9n, and 9o with better insecticidal activity was determined by electrophysiological experiments, and the mechanism of action of compound 9f 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.

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