Design, Synthesis, Characterization, Toxicological Effects, and Molecular Docking Insights of Some Novel Quinoline...

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.