QSAR and Docking Studies on 1,2-benzisoxazole Derivatives for Antipsychotic activity against Dopamine receptor (D2)

With a view to the rational design of a series of selected 48 substituted benzisoxazoles, 3D-QSAR and docking studies have been performed for the prediction of antipsychotic activity. Overall model classification accuracy was 76.00% (q2 = 0.7600, representing internal validation) in training set and 68.33% (Pred_r2 = 0.6833, representing external validation) in test set using sphere exclusion and forward–backward as a method of data selection and variable selection, respectively. The docking studies suggest that compound 38 interact with GLU43, THR48, GLN79, GLN147, LEU148, ASN149, ASP150, SER151, ARG178, LYS270, LEU273, THR327, GLU43, GLN79, GLN147, ASN149, ASP150, SER151 and GLU43 amino acid residues. Both QSAR and docking study of such derivatives provide guidance for further lead optimization and designing of more potent antipsychotic agents.