Design, synthesis, and insecticidal potency of novel 3-methyl-pyrazole derivatives against Culex pipiens larvae

= 52.90 µg/mL). Complementary in silico analyses, including molecular docking and molecular dynamics (MD) simulations, were employed to elucidate the mode of action of the synthesized compounds. Docking studies were performed for all nineteen 3-methyl-pyrazole derivatives against two principal neural targets: acetylcholinesterase (AChE), the enzyme responsible for acetylcholine degradation, and the nicotinic acetylcholine receptor (nAChR), a major ligand-gated ion channel involved in synaptic transmission. To further examine binding stability, MD simulations were conducted only for the two most active derivatives (7 and 12) in complex with AChE, using chlorpyrifos as a reference ligand. The simulations confirmed that the active compounds formed stable and persistent interactions within the catalytic site, consistent with a neurotoxic mechanism involving inhibition of AChE. Structure-activity relationship (SAR) analysis further identified functional groups contributing to potency. Overall, this preliminary investigation establishes a computational and experimental foundation for future optimization, toxicological validation, and eventual field application of next-generation larvicides designed to mitigate resistance and control mosquito-borne diseases.