Introduction: Introduction:
Chronic leukemia is a common hematological malignancy in which overexpression of anti-apoptotic proteins such as Bcl-2 and ABCB1 protein plays a key role in drug resistance. Natural compounds are considered promising sources of anticancer agents. This study aimed to investigate the inhibitory potential of selected natural compounds against these proteins using molecular docking.
Methods: Methods:
The 3D structures of Bcl-2 and ABCB1 were retrieved from the Protein Data Bank and prepared for docking. A set of natural compounds from the ZINC15 database were docked using AutoDock Vina. Binding free energy (ΔG) and clustering of poses (RMSD were analyzed to evaluate binding affinity and stability.
Results: Compounds such as ZINC000008552018 and the ZINC0000496000x family showed the strongest binding affinities toward both proteins (ΔG ≈ −9.0 to −8.3 kcal/mol). While some ligands exhibited strong affinities with multiple orientations (multi-modal binding), the ZINC0000496000x family presented convergent and stable low-energy poses. Comparative docking indicated that certain compounds could potentially interact with both Bcl-2 and ABCB1 simultaneously.
Conclusion: Conclusion:
Selected natural compounds demonstrated promising inhibitory potential against Bcl-2 and ABCB1 proteins, suggesting their role as dual modulators. These findings warrant further validation through molecular dynamics simulations and experimental studies to support the development of novel therapeutic approaches for chronic leukemia.