Gomes_2025_Pestic.Biochem.Physiol_214_106570

Managing Euschistus heros is increasingly challenging due to insecticide resistance, limited available molecules, and environmental and health concerns. Here, we synthesized and evaluated mucochloric acid derivatives as alternative tools for controlling this pest. We assessed the selectivity of these molecules toward the pollinators bees Apis mellifera and Partamona helleri and conducted in silico predictions for the interactions of these molecules with receptors for gamma-aminobutyric acid (GABARs) and nicotinic acetylcholine receptors (nAChRs), and the enzyme acetylcholinesterases (AChE) of E. heros and pollinator bees. We synthesized the lactone 3,4-dichlorofuran-2(5H)-one (13) (87 % yield) by reducing mucochloric acid (1) with sodium borohydride. We subjected mucochloric acid to etherification with nine alcohols in the presence of (S)-camphorsulfonic acid, giving rise to ethers 2-9 (60-70 % yields). Esterification of mucochloric acid with acetic and hexanoic anhydrides afforded esters 10-11 (60 % yield). Reaction with methyl chloroformate afforded compound 12 (60 % yield). Compounds 1 (LC(50) = 0.016 microg/cm(2)), 2 (LC(50) = 0.012 microg/cm(2)), and 11 (LC(50) = 0.015 microg/cm(2)) effectively controlled E. heros third instar nymphs. These molecules showed lower toxicity without affecting the feeding capacities of both pollinator bee species. The molecular predictions for the three potential targets revealed more stable interactions of the mucochloric acid derivatives with E. heros-related nAChRs compared to pollinator-associated receptors, suggesting a higher contribution of nAChR to these molecules' toxicity and selectivity. Collectively, our findings highlight the potential and environmental safety of mucochloric acid derivatives for the integrated management of stink bugs like E. heros.