Pharmacophore Identification and QSAR Studies on Substituted Benzoxazinone as Antiplatelet Agents: kNN-MFA Approach

The three-dimensional quantitative structure–activity relationship (3D-QSAR) and pharmacophore identification studies on 28 substituted benzoxazinone derivatives as antiplatelet agents have been carried out. Multiple linear regression (MLR) method was applied for QSAR model development considering training and test set approaches with various feature selection methods. Stepwise (SW), simulated annealing (SA) and genetic algorithm (GA) were applied to derive QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. The results of pharmacophore identification studies showed that hydrogen bond accepters, aromatic and hydrophobic, are the important features for antiplatelet activity. The selected best 3D kNN-MFA model A has a training set of 23 molecules and test set of 5 molecules with validation (q²) and cross validation (pred_r²) values 0.9739 and 0.8217, respectively. Additionally, the selected best 3D QSAR (MLR) model B has a training set of 23 molecules and test set of 5 molecules with validation (r²) and cross validation (pred_r²) values of 0.9435 and 0.7663, respectively, and four descriptors at the grid points S_123, E_407, E_311 and H_605. The information rendered by 3D-QSAR models may lead to a better understanding and designing of novel potent antiplatelet molecules.