In this study, an attempt was made to develop the docking studies of series of substituted thiazole analogs with cyclo-oxygenase-2 (COX-2) inhibitor (PDB-code 1CX2) to identify potential candidates with minimum dock score for anti-inflammatory activity. Molecular docking analysis was carried out to better understand the interactions between 1CX2 target and inhibitors in this series. Hydrophobic and hydrogen bond interactions lead to identification of active binding sites. A set of eleven novel substituted thiazole analogs with anti-inflammatory activity was subjected to the two dimensional quantitative structure activity relationships (2D QSAR) studies using MDS 4.0. Drug designing module with various combinations of thermodynamic, electronic and spatial descriptors. 2D QSAR was performed using Multiple Regression (MR), Principal Component Regression (PCR), partial least squares regression (PLS) method. The best 2D-QSAR model (r2 = 0.99, Fisher test value F=4549.12, r2 se =0.25) has acceptable statistical quality and predictive potential as indicated by the value of cross validated squared correlation coefficient (q2=0.92) by stepwise forward multiple regression (model-1), (r2 =0.9828, F =171.5722, r2 se =2.2614, q2 = -0.1954) by stepwise forword partial least squares regression (model-2), ( r2 =0.9825, F = 168.6592, r2 se =1.0488, q2 = 0.9454) by genetic algorithm principle component regression (model-3). From this 3 model, it seems to be clear that chiV5chain, chiV4pathCluster, T_2_N_2, T_2_S_0, T_2_S_7, T_C_N_5, T_T_O_2 contribute positively and 4pathClusterCount contribute negatively for anti-inflammatory activity. Thus this validated model brings important structural insight to aid the design of novel anti-inflammatory agent with potent compound.
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