Screening and structure–activity relationship analysis of benzoate repellents against Solenopsis invicta targeting odorant‐binding protein GP ‐9

BACKGROUND: Benzoate esters possess significant potential as broad-spectrum, environmentally friendly insecticides or repellents. However, the efficacy of methyl benzoate derivatives in pest control remains underexplored. This study systematically evaluated the repellent activities of 14 benzoate compounds and the positive control, N,N-diethyl-3-methylbenzamide (DEET), against the red imported fire ant. Additionally, molecular docking was integrated to investigate potential binding modes. RESULTS: Molecular docking results indicated favorable binding affinities to GP-9, with active molecules establishing stable hydrogen bonds and hydrophobic interactions. Multiple-choice digging bioassays demonstrated that all tested compounds possessed repellent activity. Three derivatives bearing an ortho-amino substituent exhibited superior efficacy. Among these, butyl 2-aminobenzoate displayed the highest activity with a minimum effective concentration of only 0.09 mM, significantly outperforming DEET (6 mM). Structure-activity relationship analysis revealed that the presence of an ortho-amino group (hydrogen bond donor) and elongated ester side chain (increasing lipophilicity) were critical for high potency. Furthermore, butyl 2-aminobenzoate maintained persistent repellency for 60 to 70 days. CONCLUSION: Our findings demonstrate that benzoate esters are characterized by high efficiency, low toxicity, and long-lasting effects. They hold great potential as alternatives to conventional high-toxicity insecticides for quarantine interception and management of S. invicta in sensitive areas. © 2026 Society of Chemical Industry.