Evaluation of New Coumarins for Anti-Cancer Activity in HL-60 Cell Line Supported by Molecular Docking, MD Simulation, and Binding Free Energy Calculations

Introduction: Leukemia, a prevalent malignancy characterized by chromosomal aberrations, was targeted in this study to assess the anti-cancer potential of naturally isolated novel coumarins. Methods: ) were assessed against HL-60 leukemia cells using in vitro and in silico approaches. Results: The MTT assay demonstrated significant cytotoxicity of the compounds against HL-60 cells. Molecular docking studies revealed strong binding interactions with CDK-2 and BCL-2 proteins, supporting the in vitro results. Compound 2 exhibited the highest binding energy with CDK-2. Molecular dynamics simulations, binding free energy calculations, principal component analysis (PCA), and free energy landscape analyses were performed to assess the stability of the Compound 2-CDK-2 complex. The results indicated that the complex remained stable during the MD simulation with favorable binding free energies. ADMET predictions confirmed favorable pharmacokinetic profiles and safety from hERG blockade. Conclusion: These findings highlight the compounds' promising pharmacological activity and potential for further drug development, though additional studies are needed to explore their clinical applications.