Comparative Pharmacophore Modeling and QSAR Studies for Structural Requirements of some Substituted 2-Aminopyridine Derivatives as Inhibitors of Nitric Oxide Synthases
The present study is an attempt in this direction seeking for the development and comparison of QSAR models of substituted 2-aminopyridine derivatives as inhibitors of nitric oxide synthases by different feature selection methods. The QSAR study was carried out on V-life Molecular Design Suite software, and the derived best QSAR model was derived by partial component regression method. The statistically significant best model with high correlation coefficient (\(r^{2}=0.8408\)) was selected for further study. The model was further validated by means of crossed squared correlation coefficient (\(q^{2}=0.7270\) and \(\hbox {pred}\_r^{2}=0.7889\)) which shows model has good predictive ability. The best 3D-QSAR model showed \(q^{2}=0.8377,\,r^{2} = 0.8739\) and standard error=0.1954. The predictive ability of the resultant model was evaluated using a test set molecules and the predicted \(r^{2}=0.8159.\) The results reveal that the acceptor, donor, aliphatic, and aromatic pharmacophore properties are favorable contour sites for both the activities. The two-dimensional and k-nearest-neighbor contour plots were required for further understanding of the relationship between structural features of substituted 2-aminopyridine derivatives and their activities which should be applicable to design newer potential inducible nitric oxide synthases.
pharmacophore nitric oxide synthases pyridines quantitative structureactivity relationship (qsar) molecular field analysis partial component regression (pcr)