Design, synthesis and bioactivity of cyclic dinucleotides against Lepidoptera insects

Abstract

Cyclic dinucleotides (CDNs) play important physiological roles in bacteria, mammals and insects as a novel class of signaling molecules. However, the application of CDNs in agricultural pest control has not been reported yet. To explore the potential bioactivity of CDNs on agricultural pests, we synthesized ten kinds of CDNs containing adenine and guanine bases with different internucleotide linkages (3′,3′; 2′,3′; 2′,2′). The target CDNs were used to determine the antifeedant and insecticidal activity against common Lepidoptera pests including S. frugiperda, M. separata, and H. armigera. The bioassay tests indicated that 3′,3′-c-di-AMP showed the highest antifeedant activity (EC₅₀ = 0.59 mg/L) against M. separata larvae among all the tested CDNs. Regarding insecticidal activity, 2′,3′-c-di-AMP showed higher insecticidal activity against M. separata larvae with LC₅₀ of 55.4 mg/L. RNA-seq further revealed that 3′,3′-c-di-AMP and 2′,3′-c-di-AMP exhibited a significant effect on the growth and development process of insects. More importantly, the bioactivity of 3′,3′-c-di-AMP was also closely correlated with the stimulation of insect immune inflammation. These results indicated that cyclic dinucleotides can affect the normal physiological process of insects, providing a new direction for managing pests.