2D QSAR STUDY OF INDOLE DERIVATIVES AS SELECTIVE COX-2 INHIBITORS

The NSAIDs are popular in reducing acute and chronic inflammation as they have no abuse liability. QSAR (Quantitative structure-activity relationship) approach is a very useful and widespread technique for drug design. 2D QSAR models are based on descriptors derived from a two-dimensional graph representation of a molecule. The 2D QSAR study was performed on selected twenty-four compounds from synthesized indole derivatives for elucidating the structural requirements for COX-2 inhibition using multiple linear regression method. Statistically, significant models were generated using VLife Molecular Design Suite 3.5 software. The physicochemical parameters contributed significantly to biological activity. Amongst all the models generated, model 3 was found to be best with high r² (squared correlation coefficient) of 0.9382. Model is robust as q² (cross-validated squared correlation coefficient) value is also high as 0.8557 with good predictive power as indicated by pred_r² = 0.7443. The model showed two alignment independent (AI) descriptors T_2_O_0 and T_2_N_7 as well as two physicochemical descriptors –ve Potential Surface Area and SA Most Hydrophobic contributing for activity. 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.