Evaluation of New Coumarins for Anti-Cancer Activity in HL-60 Cell Line Supported by Molecular Docking, MD...

Leukemia, a prevalent malignancy characterized by chromosomal aberrations, was targeted in this study to assess the anti-cancer potential of naturally isolated novel coumarins.

Novel coumarins (isolated from the natural source Sterculia colorata) were assessed against HL-60 leukemia cells using in vitro and in silico approaches.

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.

These findings highlight the compounds' promising pharmacological activity and potential for further drug development, though additional studies are needed to explore their clinical applications.