Molecular Docking and Toxicity Prediction of Artocarpus heterophyllus Compounds as Anti-Pancreatic Cancer Agents
Keywords:
Artocarpus heterophyllus; Pancreatic cancer; PPARγ; Molecular docking; Toxicity predictionAbstract
Background: Pancreatic cancer is a highly aggressive cancer with increasing incidence and poor survival rates. Current therapies like gemcitabine show limited efficacy and cause significant toxicity. Natural compounds from Artocarpus heterophyllus have demonstrated diverse pharmacological properties, including anticancer potential, making them promising candidates for alternative treatments.
Objective: This study aims to evaluate the anti-pancreatic cancer potential of Artocarpus heterophyllus compounds targeting PPARγ using molecular docking and toxicity prediction.
Research methods: The PPARγ protein (PDB ID: 3U9Q) was prepared and refined for docking simulations. Six compounds from A. heterophyllus and gemcitabine were docked using AutoDock Vina to assess binding affinities. Interaction profiles were visualized to identify key residues involved. Toxicity parameters including hepatotoxicity, carcinogenicity, and immunotoxicity were predicted using ProTox-3 to evaluate safety profiles.
Results: Quercetin exhibited the strongest binding affinity –7.6 kcal/mol, surpassing gemcitabine –5.4 kcal/mol and native ligand decanoic acid –5.8 kcal/mol. Myricetin and cintriamide also showed favorable binding energies –5.9 and –7.0 kcal/mol. Quercetin and myricetin had low predicted toxicity, including non-hepatotoxic and non-mutagenic profiles, supported by previous hepatoprotective evidence. Cintriamide displayed strong binding but raised immunotoxicity concerns. Artocarpesin and licoflavone C showed weaker binding yet low toxicity. Key interactions involved residues Ser289, Cys285, and Phe363, critical for ligand stability.
Conclusion: Artocarpus heterophyllus compounds, especially quercetin and myricetin, demonstrate promising anticancer activity against pancreatic cancer with favorable safety profiles.
Keywords: Artocarpus heterophyllus; Pancreatic cancer; PPARγ; Molecular docking; Toxicity prediction
