Early-Stage Screening of Piperonylic Acid Analogues and Their Salts as Synergists for the Class of Pyrethroid Insecticides.

This study presents an early-stage screening of piperonylic acid analogues and their salts as synergists for the class of pyrethroid insecticides. Using the carbonate-based ionic liquid synthesis (CBILs) method, we synthesized 32 potential synergists from 4 piperonylic acid analogues in a one-step process and experimentally determined general toxicity parameters and synergistic activity in comparison with the commercial synergist piperonyl butoxide (PBO). In vitro assays revealed structure-dependent activity of synergists on detoxification enzymes of Blattella germanica, with several candidates demonstrating similar or even higher activity compared to PBO. Subsequent in vivo testing of selected compounds confirmed their overall synergistic potential but showed lower activity than PBO, underscoring the need to validate in vitro findings in vivo. The reported synergistic activity of piperonylic acid analogues and the ability for noncovalent modification can act as a starting point for future structure optimization to find alternatives for PBO in pyrethroid insecticide formulations.