In Silico Screening of Plant-Derived Termiticidal Compounds Targeting Cytochrome P450 in Coptotermes spp. (Blattodea: Rhinotermitidae) for Sustainable Termite Management

Termites of the genus Coptotermes are among the most destructive structural pests worldwide, owing to their efficient lignocellulose degradation and metabolic adaptability mediated in part by cytochrome P450 enzymes. Although numerous botanical compounds have been reported to exhibit termiticidal activity, mechanistic in silico studies targeting detoxification-related enzymes in Coptotermes, particularly cytochrome P450, remain limited. In this study, twenty-eight plant-derived bioactive compounds were evaluated using an integrated in silico framework comprising insecticide likeness screening, molecular docking, toxicity prediction, environmental fate assessment, and molecular dynamics simulation. Homology modeling enabled structural characterization of cytochrome P450 from C. formosanus, and subsequent screening identified 27 compounds with favorable physicochemical and ADMET properties. Molecular docking analysis highlighted Glyceollin, Cnicin, Biochanin A, Ferruginol, and ent-kaur-16-en-19-oic acid as strong binders, exhibiting stable interactions with conserved active-site residues. Toxicological and ecological assessments indicated generally low predicted risk to mammals, birds, and pollinators, while identifying potential sensitivity in aquatic organisms, emphasizing the need for controlled application. Molecular dynamics simulations further supported the stabilizing effect of Glyceollin on cytochrome P450 under simulated conditions. Overall, the study provides mechanistic insight into botanical inhibition of cytochrome P450 in Coptotermes and identifies promising candidate compounds for further experimental validation in sustainable termite management strategies.