3D QSAR AND DOCKING STUDY OF INDOLE DERIVATIVES AS SELECTIVE COX-2 INHIBITORS
- Vol.11(4)
- M P Innovare Academic Sciences Pvt Ltd 2019
- 84-92p.
Objective : Non-steroidal anti-inflammatory agents (NSAIDs) con tinue to be one of the most widely used groups of t herapeutic agents. QSAR (quantitative structure-activity relationship) appr oach 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' valu es with the activity. Methods : 3D QSAR study was performed on selected twenty-four compounds from synthesized indole derivatives usin g the stepwise variable selection k-nearest neighbor (kNN) molecular field analysis approach for indicating the contribution o f the steric and electronic field for activity. The docking study was performed to further confirm the binding affinity of synthesized molecules (liga nds) 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 cro ss-validated correlation coefficient q 2 of 0.9461 and high predictive correlation coefficie nt (Pred_r 2 ) of 0.8782 indicating that the model is robust. Th e results of docking study suggest that the synthesized compounds have a comparable bi nding affinity with the COX-2 enzyme. Conclusion : The present study may prove to be helpful in the de velopment and optimization of existing indole deriv atives as anti-inflammatory agents with selective COX-2 inhibition.