Abstract
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: Novel coumarins (isolated from the natural source Sterculia colorata) 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.