3D QSAR AND DOCKING STUDY OF INDOLE DERIVATIVES AS SELECTIVE COX-2 INHIBITORS
Objective: Non-steroidal anti-inflammatory agents (NSAIDs) continue to be one of the most widely used groups of therapeutic agents. QSAR (quantitative structure-activity relationship) approach is a very useful and widespread technique for drug design. 3D QSAR facilitates evaluation of three-dimensional molecular fields around molecules and generates a relationship of these fields' values with the activity.
Methods: 3D QSAR study was performed on selected twenty-four compounds from synthesized indole derivatives using the stepwise variable selection k-nearest neighbor (kNN) molecular field analysis approach for indicating the contribution of the steric and electronic field for activity. The docking study was performed to further confirm the binding affinity of synthesized molecules (ligands) to COX-2 enzyme as well as to study binding nature.
Results: Statistically significant model was generated using VLife Molecular Design Suite 3.5 software with cross-validated correlation coefficient q2 of 0.9461 and high predictive correlation coefficient (Pred_r2) of 0.8782 indicating that the model is robust. The results of docking study suggest that the synthesized compounds have a comparable binding affinity with the COX-2 enzyme.
Conclusion: The present study may prove to be helpful in the development and optimization of existing indole derivatives as anti-inflammatory agents with selective COX-2 inhibition.
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