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

TL;DR

This study identifies plant-based compounds that may effectively target termite enzymes, offering a sustainable pest control solution with low risk to non-target species.

Contribution

The study introduces novel plant-derived compounds targeting cytochrome P450 in termites through integrated in silico methods.

Findings

Twenty-seven plant-derived compounds showed favorable properties for targeting cytochrome P450 in Coptotermes.

Glyceollin and other compounds exhibited strong binding to cytochrome P450 active-site residues.

The compounds showed low predicted risk to mammals and pollinators but potential sensitivity in aquatic organisms.

Abstract

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.

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