Computational and In Vitro Evaluation of Plumbagin and Griseofulvin as Natural PIM1 Kinase Inhibitors for Potential Anticancer Therapy

The rising global incidence of cancer, coupled with the limitations of current treatments, underscores the need for novel therapeutic agents. This study investigates the anticancer potential of natural compounds, focusing on identifying and characterizing underexplored molecules with promising pharmacological properties. QSAR modeling identified plumbagin and griseofulvin as lead compounds with potent cytotoxicity across various cancer cell lines, including breast, colon, liver, lung, and leukemia. In vitro assays revealed dose‐dependent cytotoxic effects, with plumbagin showing IC 50 values of 4.13 (HepG2) and 8.74 µM (A549), while griseofulvin exhibited IC 50 values of 44.76 and 26.3 µM, respectively. ADME and toxicity profiling confirmed their drug‐likeness, compliance with Lipinski's rule, and high oral bioavailability (>96%). Annexin V assays further supported their anticancer potential. Target prediction identified PIM1 kinase as a common key molecular target. Molecular docking and dynamics simulations revealed stable, thermodynamically favorable binding, with binding free energies of −14.71 kcal/mol (plumbagin) and −19.58 kcal/mol (griseofulvin). These findings suggest both compounds are promising PIM1 inhibitors, capable of modulating oncogenic pathways. This study underscores the therapeutic potential of natural compounds in targeted anticancer drug development. Further in vivo studies are essential to confirm the efficacy and safety of these compounds.