Design, Synthesis, Characterization, Toxicological Effects, and Molecular Docking Insights of Some Novel Quinoline Compounds as Potential Insecticides

Abstract

In the pursuit of novel insecticidal agents, a series of new thieno[2,3-b]quinoline derivatives were synthesized via efficient and versatile routes, starting from ethyl 3-aminothieno[2,3-b]quinoline-2-carboxylate. The synthesized compounds including hydrazone (8a–c), arylidene (9a–c), and pyrano[3,2-c]thieno[2,3-b]quinoline (10a–c) derivatives were characterized using FT-IR, NMR, and mass spectrometry. Their insecticidal efficacy was evaluated against both nymph and adult stages of Aphis fabae, with median lethal concentration (LC50) values determined through probit analysis. Compound 10b exhibited the highest potency, with LC50 values of 0.117 mg/L (nymphs) and 0.366 mg/L (adults), approaching the activity of the commercial insecticide acetamiprid. Molecular docking studies against the Aplysia californica acetylcholine-binding protein (AChBP, PDB: 3SQ6), a surrogate for insect nicotinic acetylcholine receptors, revealed strong binding affinities for the pyranothienoquinoline derivatives, particularly 10b (−7.30 kcal/mol), supported by multiple hydrogen bonds and hydrophobic interactions with key residues. These findings underscore the potential of the pyrano[3,2-c]thieno[2,3-b]quinoline scaffold as a promising candidate for the development of new, target-specific insecticides.