LC-MS-Based Metabolite Profiling and Integrated in Silico Lead Optimization of Lablab purpureus L. (Sweet) Seed Coat Metabolites Targeting Human Papillomavirus Type 16 (HPV16) E6 Oncoprotein for Cervical Cancer Therapy

Abstract

Background: Persistent HPV16 infection promotes cervical carcinogenesis primarily through E6-mediated p53 degradation. Natural-product leads from agricultural by-products remain insufficiently explored for targeting this viral oncoprotein. Objective: This study profiled secondary metabolites in the seed coat of Lablab purpureus and evaluated their potential as candidate ligands against HPV16 E6 using an integrated computational workflow. Methods: A crude methanolic seed-coat extract was analysed by untargeted LC-MS/MS. Annotated constituents were docked against HPV16 E6 (PDB ID: 4GIZ) with AutoDock Vina/PyRx. The leading compounds were assessed using ADMET prediction, while lupeol was further examined by density functional theory calculations. Results: LC-MS/MS tentatively identified 36 phytoconstituents across positive and negative ion polarities. Pentacyclic triterpenoids showed the strongest predicted binding affinities, with lupeol and ursolic acid yielding scores of −10.2 and −9.9 kcal/mol, respectively. Lupeol formed mainly hydrophobic contacts, whereas ursolic acid showed hydrogen-bonding and hydrophobic interactions within the predicted binding region. Both compounds had high predicted intestinal absorption and no PAINS or Brenk alerts, but their high lipophilicity, poor aqueous solubility, Lipinski violations, and computational toxicity signals indicated important development constraints. Lupeol had a calculated HOMO–LUMO energy gap of 0.2593 eV. Conclusion: The seed coat contained diverse metabolites, and lupeol and ursolic acid were prioritised as computational candidates for further experimental evaluation against HPV16 E6. Chemical confirmation, binding assays, cellular validation, pharmacokinetic studies, and toxicity testing remain necessary.