Eco-Friendly Pectin-Derived Heterocycles as Potent Larvicides: Biochemical and Insecticidal Insights Against Culex pipiens With Computational Investigation.

Mosquito-borne diseases remain a public-health concern, creating an urgent need for safer and biodegradable alternatives to conventional insecticides. In this study, pectin was chemically modified to prepare pectin hydrazide, pectin oxadiazole, and pectin triazole derivatives as eco-friendly heterocyclic biopolymer-based larvicides. Structural modification was confirmed by spectroscopic, thermal, and morphological characterization. Larvicidal activity was evaluated against third-instar Culex pipiens larvae after 24 and 48 h of exposure. Mortality increased in a concentration- and time-dependent manner, with pectin hydrazide showing the highest activity after 48 h and an LC50 of 0.31 ppm, followed by pectin oxadiazole (0.52 ppm) and pectin triazole (0.55 ppm). Biochemical assays showed changes in total protein, lipid, and carbohydrate contents, together with ATPase inhibition and increased glutathione S-transferase activity, indicating disruption of energy metabolism, membrane-associated processes, and detoxification responses. Molecular docking and molecular dynamics simulations supported favorable interactions and stable binding with selected insect-related protein targets, while DFT calculations provided insight into electronic properties and potential reactive sites. Overall, these findings highlight pectin-derived heterocycles as promising renewable candidates for environmentally compatible larvicidal development against C. pipiens. The integrated experimental and computational results demonstrate that chemical functionalization of pectin can enhance larvicidal performance while retaining a renewable biopolymer platform.