Uncovering Anti-Cancer Potential of Clausena anisata Bioactives via Network Pharmacology-Based Target Prediction, Virtual Screening, Docking, ADMET Analysis, and Molecular Dynamics Simulation

Abstract Introduction: Despite advances in oncological interventions, multidrug resistance and severe toxicity drive the need for novel, cost-effective therapeutic agents. Clausena anisata is a phytochemically rich plant with antineoplastic properties; however, its targets and mechanisms remain poorly understood. To bridge this gap, we utilized integrated network pharmacology and computer-aided drug design (CADD) to elucidate the multitarget anticancer potential of Clausena anisata bioactives. Materials and Methods For this study, an integrated computational method (network pharmacology, molecular docking, ADMET profiling, molecular dynamics (MD) simulation, and MM-PBSA analysis) screened lead compounds of Clausena anisata for cancer treatment. 69 phytochemicals were screened using SwissADME. SwissTargetPrediction predicted protein targets, compared with cancer-associated genes from GeneCards. STRING and Cytoscape analyzed protein-protein interaction networks. Results ADMET screening identified seven pharmacokinetic, drug-like compounds adhering to Lipinski, Ghose, Veber, Egan, and Muegge rules, violation-free. Target prediction identified 247 targets; network analysis revealed EGFR as hub. Anisolactone (IMPHY000449) and Triphasiol (IMPHY001745) docked to EGFR, with LibDock scores 116.89 and 116.23, near AG4 (121.43). Complexes remained stable during 100 ns dynamics simulations, with RMSD, RMSF, and free energy landscape plots.MM-PBSA calculated energies of − 28.49 ± 1.25 kcal/mol and − 24.10 ± 1.18 kcal/mol. Compounds showed gut absorption and no PAINS flags. Discussion These data collectively indicate that Anisolactone and Triphasiol are promising lead compounds with anticancer properties. By effectively targeting the EGFR, these compounds may in turn inhibit the growth of other proteins involved in cancer progression. Conclusion The computational findings provide a robust foundational mechanism, thereby justifying additional in vitro and in vivo studies on Clausena anisata .