Rational design and multidimensional profiling of polyfluorinated pyrethroids: a resistance‐breaking strategy for next‐generation mosquito vector control

Abstract BACKGROUND Pyrethroids based on chrysanthemic acid are widely used for mosquito control due to their high potency and low mammalian toxicity. However, growing resistance and environmental concerns necessitate new analogues. This study designed novel polyfluorinated pyrethroids derived from chrysanthemic acid scaffolds to overcome resistance, reduce ecotoxicity, and improve photostability. RESULTS Fourteen of 54 synthesized chrysanthemate‐based compounds exceeded bifenthrin (LC 50 = 1.96 mg/L) against sensitive mosquitoes. Lead compounds BFA‐3‐1 , BFA‐3‐2 , and BFA‐3‐4 showed LC 50 values of 0.55, 0.45, and 0.53 mg/L, respectively, and were 5–7 times more potent against resistant strains than deltamethrin. They also exhibited 10‐fold lower acute toxicity to zebrafish (96 h‐LC₅₀ = 0.47–0.67 mg/L) and longer photodegradation half‐lives (108–133 min under simulated sunlight). CONCLUSION Chrysanthemic acid‐based polyfluorinated pyrethroids effectively break resistance, reduce non‐target toxicity, and maintain photostability, offering a sustainable chemical template for next‐generation vector control. © 2026 Society of Chemical Industry.