Development of Novel (+)-Nootkatone-Fused Thiazolidine Derivatives as Potent Insecticide Candidates.

To discover novel insecticide candidates, herein, a series of novel (+)-nootkatone derivatives were synthesized by introducing a thiazolidine moiety into (+)-nootkatone. Among them, compound 9x was identified as the most active candidate, with a final corrected mortality rate of 66.7% against Mythimna separataand an LC50 value of 0.21 mg/mL against Plutella xylostella, outperforming positive controls toosendanin and rotenone. Moreover, in pot experiments, 9x and 9p demonstrated a significant control efficacy against P. xylostella. Mechanism studies indicated that 9x effectively inhibits glutathione S-transferase (GST) activity for P. xylostella, while it has no significant effects on carboxylesterase (CarE). Additionally, molecular docking further revealed strong binding interactions between 9x and the GST. Finally, toxicity test results indicated that 9e, 9p, and 9x exhibit significantly lower toxicity to non-target organisms than rotenone does, demonstrating good safety. Collectively, 9x holds promise as a novel green insecticide with high efficacy and low toxicity, offering favorable prospects for further development.