Three-Dimensional Quantitative Structure-Activity Relationships and Molecular Dynamic Simulations Studies to Discover Aurora Kinase-B Inhibitors

The serine-threonine kinase gene Aurora–B kinase plays a critical role in spindle assembly, chromosome alignment, mitotic checkpoint activation, and cytokinesis. The overexpression of Aurora-B causes errors in cell division and multinucleation in centrosome numbers leads to cancer. Three–dimensional Quantitative Structure-Activity Relationship studies were conducted on known inhibitors to find valid pharmacophore hypotheses. The five features hypothesis AADRR with better parameters using partial least square analysis has been selected for virtual screening. Molecular docking was applied to find the binding mode interactions of ligands with the Aurora-B binding pocket. Lys 106, Ala 157, Glu 161, and Phe 219 were identified as crucial residues that formed several interactions with the ligands which are essential for Aurora–B inhibition. After the different levels of screening, five compounds from the National Cancer Institute database were acknowledged as novel inhibitors of Aurora–B. The active site interactions of the protein-ligand complex were examined by molecular dynamics simulation studies. Graphical Abstract