Development of new CoMFA and CoMSIA 3D-QSAR models for anti-inflammatory phthalimide-containing TNFα modulators Original Research Article

In the present study, we describe a new 3D-QSAR analysis of 42 previously reported thalidomide analogues, with the ability to modulate the pro-inflammatory cytokine TNFα, by using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Three statistically significant models were obtained. The best resulting CoMFA and CoMSIA models have conventional r2 values of 0.996 and 0.983, respectively. The cross-validated q2 values are 0.869 and 0.868, respectively. The analysis of CoMFA and CoMSIA contour maps provided insight into the possible sites for structural modification of the thalidomide analogues for better activity and reduced toxicity.