Enantioselective endocrine-disrupting effects of the phenylpyrazole chiral insecticides in vitro and in silico

Abstract The phenylpyrazole chiral insecticides, including the widely used fipronil, ethiprole, and flufiprole, have generated a worldwide interest due to their environmental toxicity. However, up to now,only few studies focused on their their potential endocrine-disrupting effects (EDEs). In this study, we investigated the endocrine hormonal disorder caused by the fipronil, ethiprole, and flufiprole enantiomers in vitro and in silico approach. Results of the luciferase reporter assay indicated that the enantiomers of fipronil, ethiprole, or flufiprole have shown stereoselective endocrine-disrupting effects. S-(−)-ethiprole and S-(−)-flufiprole have anti-thyroidal disorder effects whereas R-(−)-fipronil, R-(+)-ethiprole, and R-(+)-flufiprole showed anti-estrogenic disorder effects. The results of the molecular dynamics simulations revealed that the happened EDEs could be partially attributed to the enantioselective specific receptor binding affinities. It also suggested that van der Waals interactions plays an important role in the binding procedure. This study could provide helpful information for the explanation of enantioselectivity in the EDEs of chiral phenylpyrazole pesticides at the molecular level.