QSAR Studies on Aminothiazole Derivatives as Aurora A Kinase Inhibitors

Abstract

Quantitative structure-activity relationship studies on 54 aminothiazole derivatives as Aurora A kinase inhibitors were performed to explore the important factors affecting their biologic activity. For 2D-quantitative structure-activity relationship study, genetic algorithm combined with multiple linear regression was used to select significant molecular descriptors. The MLR model gave squared correlation coefficient of 0.828 and squared cross-validated correlation coefficient of 0.771 for the training set compounds. Comparative molecular field analysis and comparative molecular similarity indices analysis were used to develop 3D-quantitative structure-activity relationship models. The comparative molecular field analysis model gave cross-validated correlation coefficient q 2 of 0.695 and non-cross-validated correlation coefficient r 2 of 0.977. For comparative molecular similarity indices analysis model, the corresponding q 2 and r 2 were 0.698 and 0.960, respectively. The proposed 3D-quantitative structure-activity relationship models were validated by the test set compounds not used in the modeling process, with r 2 pred values of 0.788 for comparative molecular field analysis and 0.798 for comparative molecular similarity indices analysis. The 3D contour maps suggested that further modification of the aniline group of compound 22 considering electrostatic, hydrophobic and hydrogen bond properties would influence the inhibitory activity. The results from quantitative structureactivity relationship models would be very useful to understand the structure-activity relationship of these inhibitors and to guide the further structural modification of new potential inhibitors.

1‐[(2‐Arylthiazol‐4‐yl)methyl]azoles as a New Class of Anticonvulsants: Design, Synthesis, In vivo Screening, and In silico Drug‐like Properties

“…On the other hand, it is well‐known that thiazole nucleus as important pharmacophore appears extensively in various types of pharmaceutical agents especially in anticonvulsant agents (17–20). Motivated by these findings, and as a part of our continuous investigation into the area of (arylalkyl)azole anticonvulsants, we designed and synthesized several new thiazole incorporated (arylalkyl)azoles (Figure 1).…”

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

“…A series of amino thiazole derivatives with Aurora kinase inhibitory properties were selected from a 54-compound dataset (Table 1) published in the literature. The pIC 50 values were transformed and used as a dependent variable [5].…”

2-Amino Thiazole Derivatives as Prospective Aurora Kinase Inhibitors against Breast Cancer: QSAR, ADMET Prediction, Molecular Docking, and Molecular Dynamic Simulation Studies

“…The molecular structures required for the study were created using ChemDraw Professional 16, and the structures were further converted into mol2 file format by using Open Babel v2.4.1.17. 50 ChemDraw Professional 16 version was used to create the molecular structures, which were then translated to the mol2 format using Open Babel v2.4.1.17. 51 When hydrogens were The molecular geometries of the compounds were optimized by using the MMFF94 molecular mechanics technique.…”

“…The molecular structures required for the study were created using ChemDraw Professional 16, and the structures were further converted into mol2 file format by using Open Babel v2.4.1.17 …”