Exploring 2D and 3D QSARs of 2,4-Diphenyl-1,3-oxazolines for Ovicidal Activity Against Tetranychus urticae

Quantitative Structure-Activity Relationship (QSAR) studies have been carried out for ovicidal activity of 2,4-diphenyl-1,3-oxazoline analogues against two-spotted spider mite Tetranychus urticae, which causes serious damage to agricultural products. The studies have been performed with 2D (physicochemical, structural, and topological) and 3D (shape, spatial, electronic, and molecular field) descriptors. The chemometrics tools used for the analyses are Genetic Function Approximation (GFA) and Genetic Partial Least Squares (G/PLS). The whole dataset (n = 90) was divided into a training set (75% of the dataset) and a test set (remaining 25%) on the basis of K-means clustering technique of standardized topological and structural descriptor matrix. Models developed from the training set were used to predict the activity of the test set compounds. All the models have been validated internally, externally, and by Y-randomization technique. However, different models emerged as the best ones according to different validation criteria. We have tried a consensus model, which is based on the results obtained by all predictive models and this may provide the most stable solution. Models obtained by using 2D parameters revealed that the chain length of the substituent at para position of the 4-phenyl ring is a critical factor. Lipophilicity of the molecule also reflects a dominant role for the ovicidal activity. Models generated from 3D descriptors suggest that the shape of the substituents should be optimum and the lipophilic substituents having electronegative atoms with distributed positive charge over a surface may enhance the ovicidal activity. The model obtained from Molecular Field Analysis (MFA) suggests that bulky substituents with optimally distributed charge may increase the ovicidal activity.