QSAR modelling, ADMET prediction, molecular docking and molecular dynamics studies of novel 2-amino thiazole derivatives as Aurora kinase inhibitors

Abstract

The Aurora kinase is implicated in tumor growth and several small medicines that target the Aurora kinase have been found to have strong anti-cancer effects. Quantitative structure-activity relationship (QSAR) studies on 2-amino thiazole compounds for Aurora kinase inhibitory action targeting breast cancer were conducted out by QSARINS in this study. With statistical values R2 = 0.6102, CCCtr = 0.7580, Q2 LOO = 0.6875, Q2LMO = 0.6624, CCCcv = 0.6535, R2ext = 0.7735 and CCCext = 0.8383. Best top two models created comprise five variables: Estate VSA5, PSA, MoRSEP3, MATSp5 and RDFC24. Atomic charges, atomic volume and Sanderson's electronegativity all play a part in the design and optimization of the lead. In silico docking study was performed AutoDock v4.2.6. There are eight novel compounds have been designed, the residues from the active site region, which contains both hydrophilic and hydrophobic regions, interacted with the best active site pockets of 1MQ4, predicted active molecules 1a, 2a, 3e, 4d, 5d and 6d. Hydrophobic and hydrophilic stable contacts were seen in the active site of compound 1a in Desmond's molecular dynamics simulation investigations lasting 100 ns. The stable binding of compound 1a with the 1MQ4 structure was verified by RMSD, RMSF, RoG, H-bond and SASA analyses. We suggest that the proposed compound 1a can be used as the best theoretical lead for further experimental investigation of selective inhibition. Furthermore, newly designed compounds exhibited good ADMET properties. The study will result in the development of new breast cancer inhibitors.