Page 105 - IMO-2-2

Innovative Medicines & Omics

ORIGINAL RESEARCH ARTICLE
Computational identification and molecular

characterization of novel Aurora-B kinase
inhibitors: Pharmacophore modeling, docking,

and molecular dynamics simulations

1
Athavan Alias Anand Selvam * , Sunil Kumar Bandral 2 ,
Parasuraman Pavadai 2 , and Kabilan Senthamaraikannan 3
1 Department of Chemistry, Prayoga Institute of Education Research, Bengaluru, Karnataka, India
2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of
Applied Sciences, Bengaluru, Karnataka, India
3 Department of Chemistry, Annamalai University, Annamalai Nagar, Tamil Nadu, India

Abstract
Aurora-B, a serine-threonine kinase, plays a critical role in spindle assembly,
chromosome alignment, mitotic checkpoint activation, and cytokinesis. The
overexpression of Aurora-B leads to abnormal cell division, multinucleation, and
centrosome amplification, contributing to cancer. To identify potential Aurora-B
inhibitors, a 3D-quantitative structure-activity relationship study was conducted,
leading to the selection of a five-feature pharmacophore model (AADRR) with
*Corresponding author: optimal partial least square parameters for virtual screening. Molecular docking was
Athavan Alias Anand Selvam
(athavan@prayoga.org.in) performed to determine the binding interactions of the candidate ligands with the
human Aurora-B: inner centromere protein complex (PDB ID: 4AF3), identifying LYS
Citation: Selvam AAA, Bandral SK,
Pavadai P, Senthamaraikannan K. 106, ALA 157, GLU 161, and PHE 219 as key residues crucial for the enzyme inhibition.
Computational identification and Based on virtual screening, pharmacokinetic properties, and docking analysis, five
molecular characterization of lead compounds were selected from the national cancer institute (NCI) database:
novel Aurora-B kinase inhibitors:
Pharmacophore modeling, Compound 1 (NCI ID: 695163), Compound 2 (NCI ID: 327359), Compound 3 (NCI
docking, and molecular dynamics ID: 721045), Compound 4 (NCI ID: 711797), and Compound 5 (NCI ID: 104546). To
simulations. Innov Med Omics. clarify the interactions between Aurora-B protein and lead compounds, molecular
2025;2(2):99-112.
doi: 10.36922/imo.6547 dynamics simulations were carried out. The results demonstrated strong interactions
between the lead compounds and critical active-site residues such as ALA 157 and
Received: November 23, 2024 LYS 106. The active site interactions of the protein-ligand complex were further
Revised: March 11, 2025
Accepted: March 18, 2025 validated through molecular dynamics simulation studies, providing insights into
Published online: April 7, 2025 their binding stability and inhibitory potential.
Copyright: © 2025 Author(s).
This is an Open-Access article
distributed under the terms of the Keywords: Aurora-B kinase; Cytokinesis; 3D-quantitative structure-activity relationship;
Creative Commons Attribution Molecular docking; Molecular dynamics simulations
License, permitting distribution,
and reproduction in any medium,
provided the original work is
properly cited.
Publisher’s Note: AccScience 1. Introduction
Publishing remains neutral with The Aurora protein family of serine/threonine kinases plays key roles in mitosis,
regard to jurisdictional claims in 1
published maps and institutional chromosome segregation, and cytokines. During mitosis, the change in the organization
affiliations. of DNA due to incorrect segregation of chromosomes and dysregulation of cell cycle

Volume 2 Issue 2 (2025) 99 doi: 10.36922/imo.6547