AURORA B KINASE-TARGETED MOLECULAR DOCKING OF NOVEL COMPOUNDS: STRUCTURE-BASED IDENTIFICATION OF POTENTIAL ANTICANCER LEADS

Abstract

Aurora B kinase is a key regulatory component of the chromosomal passenger complex and plays an essential role in chromosome segregation and cytokinesis, making it an attractive molecular target for anticancer drug discovery. In the present study, molecular docking was employed to investigate the binding potential of newly synthesized compounds Ia–Ij and IIa–IIj toward human Aurora B kinase. The crystal structure of Aurora B kinase complexed with VX-680 (PDB ID: 4AF3; 2.75 Å resolution) was retrieved from the Protein Data Bank and prepared using Accelrys Discovery Studio 2.5. The binding site was defined around the co-crystallized VX-680 inhibitor using a 9.0 Å radius sphere. The synthesized compounds were prepared by three-dimensional structure generation and energy minimization using the CHARMm force field and subsequently docked into the Aurora B kinase active site using the LibDock protocol. The docking results revealed variable binding scores across the two-compound series. Among compounds Ia–Ij, Ic exhibited the highest LibDock score of 113.463, whereas IIh showed the highest score of 112.522 among compounds IIa–IIj. The predicted binding modes of Ic and IIh demonstrated favourable accommodation within the Aurora B kinase binding pocket, with hydrogen-bonding and hydrophobic interactions contributing to their predicted ligand–receptor recognition. These findings identified Ic and IIh as the most promising candidates within the investigated series and provide a structure-based rationale for their further biological evaluation as potential Aurora B kinase-targeting anticancer agents.