Ligand-based drug design studies of different flavonoids as a potential inhibitor of BCR-ABL

Abstract

The BCR-ABL gene is found in most patients with chronic myelogenous leukemia (CML). Several clinical inhibitors have been discovered to lower the BCR-ABL-associated CML. But all these clinically practiced inhibitors are potentially harmful to the normal cells. Therefore, there is a dire need to identify such novel inhibitors that must be cost-effective, easily available, multitargeted, and less toxic to normal cells. In our study, we have identified some polyphenols as potential inhibitors of BCR-ABL. Dasatinib and Bosutinib are used as controls in our current study. In this context, thirteen flavonoids were sourced from the PubChem database to identify inhibitors targeting BCR-ABL. Molecular docking was performed using AutoDock Vina, which shows binding affinity of compounds between -6.9 to -10.5 kcal/mol. Among the tested flavonoids, Erysubin A and Baicalein showed the best binding affinities of –10.5 and –10.0 kcal/mol, respectively. These values were stronger than those of the clinical inhibitors Bosutinib (–7.9 kcal/mol) and Dasatinib (–8.7 kcal/mol), suggesting that Erysubin A and Baicalein have a greater potential to interact effectively with the target protein. Further studies have shown that Erysubin A and Baicalein have significant interactions with various residues of most sustainable amino acids. The MD simulation study indicates the stability and compactness of the protein complex with Baicalein and Erysubin A. Hence, these results supported the idea that polyphenols potentially inhibit the BCR-ABL protein, further in vitro and in vivo studies are recommended for their development as a novel target to lower the burden of CML.