Lead drug discovery from imidazolinone derivatives with Aurora kinase inhibitors

Abstract

Cancer is the second leading cause of death worldwide, and breast cancer accounts for 6.27 million cases in the year 2022. In the present study, Quantitative Structural Activity Relationship (QSAR) studies were performed on a dataset of 39 molecules of Imidazolinone analogues using in random selection using QSARINS Software. The statistically validated (R2 = 0.8429 Q2loo = 0.7558) MLR model was used to predict the bioactivity of novel leads. Moreover, high-scoring compounds were exposed to molecular docking and molecular dynamic modeling study. Intended derivatives 1–23 exhibited the anticipated bioactivity using a QSAR model. Aforementioned molecules were tested for binding affinities with the target protein and the majority of them demonstrated excellent interactions with binding pocket residues. Molecular dynamics simulations using Desmond for 100 ns of top complexes 1, 7, 9, 13 and 19 showed critical structural data concerning Aurora kinase inhibition. There were stable hydrophobic and hydrophilic interfaces in the dynamic site of compounds with a leading chemical structure. The chemical interacts to the (PDB: 1MQ4) structure in a stable way, according to RMSD, RMSF, RoG, H-bond, and SASA analysis. Furthermore, the docking results have been confirmed by MM-PBSA and MM-GBSA. Based on our findings, we reported the inclusion of the necessary structural features of imidazolinone derivatives leads to the development of the potent candidates for further development.