Synthesis of Benzo[h]quinoline derivatives and evaluation of their insecticidal activity against Culex pipiens L. larvae

Abstract

A new series of pyrrolinone and hydrazone derivatives containing a benzo[h]quinoline core was synthesized and evaluated for their insecticidal activity against Culex pipiens larvae. The synthesis involved condensation of acid hydrazide, obtained from a 2(3H)-furanone, with a variety of carbonyl compounds leading to the desired candidates. The larvicidal bioassays of the prepared compounds revealed that several derivatives exhibited potent activity, with pyrrolinone 6 showing the highest efficacy (LC50 = 0.4 μg/mL), surpassing the reference insecticide chlorpyrifos. Molecular docking and molecular dynamics (MD) simulations supported these findings, showing strong and stable binding of the synthesized compounds, particularly compound 6, to key mosquito neuroreceptors such as acetylcholinesterase (AChE). The structure-activity relationship (SAR) analysis highlighted the impact of functional groups on insecticidal potency. Additionally, in silico pharmacokinetic predictions indicated favorable ADME profiles for several derivatives, emphasizing their potential as effective mosquito control agents. It is hoped that this study might provide insights into the design of new benzo[h]quinoline-based insecticides contributing to addressing the challenge of insecticide resistance in mosquito populations by forming structures that could target multiple neuroreceptors.