In-silico Characterization of Annonacin’s Binding Affinity and Drug-Likness Against Pancreatic Ductal Adenocarcinoma (PDAC) Cancer Regulators.

PDAC remains an alarming global health challenge, with rising incidence rates. Therapeutic resistance, altered tumor microenvironments, and adaptive cellular responses continue to undermine conventional treatments which are further burdened by adverse effects like immunosuppression. Natural compounds have garnered attention for their ability to modulate PDAC pathogenesis with reduced toxicity. Annonacin, a bioactive acetogenin from Annona muricata , exhibits potent anticancer activity primarily via G1-phase cell cycle arrest and enhances oxidative stress. This study evaluated the suitability of drug annonacin which is a promising lead compound in anticancer drug development. Annonacin exhibits high lipophilicity (cLogP = 7.94) and retains a favorable topological polar surface area (TPSA = 120.5 Å 2 ), supporting membrane permeability. Safety profiling indicates no predicted risks for tumorigenicity, irritancy, or reproductive toxicity. Structure of annonacin was energy-minimized using Chem3D(v12.0). Molecular docking studies were conducted using AutoDock Tools(v4.2.6) to evaluate its interactions with tumor suppressor proteins: p53 (1TUP), p21-Activated Kinase 4 (2X4Z), and oncogene BCL2 (2W3L). The predicted free binding energies were −5.55 kcal/mol for p53, −5.47 kcal/mol for p21, and −5.86 kcal/mol for BCL2, suggesting stable interactions suggestive of tumor suppressive properties. These findings reinforce annonacin’s potential as a multitargeted anti-cancer agent upon subjection to further validation in preclinical models.