Theoretical and Experimental Study of Molecular Interactions of Fluralaner with Lipid Membranes

GASTALDI, M SALOMÉ; FELSZTYNA, IVAN; MIGUEL, VIRGINIA; SANCHEZ BORZONE, M; GARCÍA, DANIEL A.

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

AMER CHEMICAL SOC

Año: 2023 vol. 71 p. 2134 - 2142

0021-8561

Fluralaner is a relatively new insecticide belonging to the isoxazoline group, whose action mechanism involves the blocking of GABAA-receptors in the insect nervous system. Because of its high hydrophobicity, fluralaner could bioaccumulate and reach toxic local concentrations. Since there are no data available about the penetration and persistence of isoxazolines in biologicalmembranes, we intend to evaluate fluralaner permanence as a pollutant by using model membranes. We used experimental and in silico models to characterize the incorporation of fluralaner into the lipid phase at different packing states. We determined its impact in the membrane structure and organization. Our results confirm that fluralaner is capable of penetrating, holding, and accumulating in the lipid membrane and provide details on its precise location and orientation. These properties would allow fluralaner to reach high local concentrations in different membranes and organs, which could be dangerous for vertebrate organisms if its handling is not properly controlled.