Probing Baicalin as potential inhibitor of Aurora kinase B: A step towards lung cancer therapy.

Cell cycle regulators play pivotal roles as their dysregulation, leads to atypical proliferation and intrinsic genomic instability in cancer cells. Abnormal expression and functioning of Aurora kinase B (AURKB) are associated with cancer pathogenesis and thus exploited as a potential therapeutic target for the development of anti-cancer therapeutics. To identify effective AURKB inhibitors, a series of polyphenols was investigated to check their potential to inhibit recombinant AURKB. Their binding affinities were experimentally validated through fluorescence binding studies. Enzyme inhibition assay revealed that Mangiferin and Baicalin significantly inhibited AURKB activity with an IC 50 values of 20.0 μM and 31.1 μM, respectively. To get atomistic insights into the binding mechanism, molecular docking and MD simulations of 100 ns were performed. Both compounds formed many non-covalent interactions with the residues of the active site pocket of AURKB. In addition, minimal conformational changes in the structure and formation of stable AURKB-ligand complex were observed during MD simulation analysis. Finally, cell-based studies suggested that Baicalin exhibited in-vitro cytotoxicity and anti-proliferative effects on lung cancer cell lines. Conclusively, Baicalin may be considered a promising therapeutic molecule against AURKB, adding an additional novel lead to the anti-cancer repertoire. • AURKB is an attractive drug target for cancer therapy and thus targeted for the development of potential inhibitors. • We have identified mangiferin and baicalin as potent inhibitors of AURKB. • Docking and MD simulation studies suggested a strong binding and the formation of a stable protein-ligand complex. • Enzyme activity suggests that mangiferin and baicalin significantly inhibit the activity of AURKB. • Baicalin shows the cytotoxic effect on A549, which is linked to its therapeutic uses in the lung cancer. [ABSTRACT FROM AUTHOR]