Lachrymators: effect of N,N’-(cyclohexane-1,2-diyl)bis[2-bromoacetamide] on larvae of Culex quinquefasciatus and its odorant-binding proteins

Abstract

The continual transmission of various zoonotic diseases between animals and humans by Culex mosquitoes has resulted in a significant global health burden, largely due to the insect’s resistance to available insecticides. Lachrymators are known to induce short-lived sensory irritation in humans upon exposure, demonstrating selective toxicity. This study investigates the effect of N,N’-(cyclohexane-1,2-diyl)bis[2-bromoacetamide]—a structurally lachrymator-like compound—on Cx. quinquefasciatus. Using temephos as a standard, varying concentrations (100, 50, 25, and 12.5 µg/ml) of the test compound solution were screened against fourth instar larvae of Cx. quinquefasciatus in vitro, and the mortality rates were assessed after 24 and 48 h. The compound’s ability to bind an odorant-binding protein of the insect was also evaluated using standard precision and extra precision molecular docking methods, while Molecular Mechanics with Generalized Born and Surface Area Solvation was employed to validate the docking scores. Results revealed a significant time-dependent increase in the compound’s potential, with the lethal concentration-50 (LC50) value decreasing from 80 µg ml−1 at 24 h to 31 µg ml−1 at 48 h, indicating enhanced effectiveness with prolonged exposure. Docking studies of the compound with the odorant-binding protein of Cx. quinquefasciatus (PDB ID: 3OGN) demonstrated an encouraging docking score, highlighting strong selectivity and affinity for the protein compared to the standard compound.