QSAR analysis of 1,3-diaryl-4,5,6,7-tetrahydro-2H-isoindole derivatives as selective COX-2 inhibitors

Quantitative structure–activity relationship (QSAR) analysis was performed on a series of 1,3-diaryl-4,5,6,7-tetrahydro-2H  -isoindole for their cyclooxygenase-2 (COX-2) inhibition. QSAR investigations were based on Hansch's extra thermodynamic multi-parameter approach and receptor surface analysis (RSA). QSAR investigations reveal that steric and electrostatic interactions are primarily responsible for COX-2 enzyme–ligand interaction. QSAR model derived from Hansch analysis demonstrated that COX-2 inhibitory activity is correlated with sum of atomic polarizability (Apol), number of hydrogen-bond donor groups (HBD), energy of the highest occupied molecular orbital (HOMO), desolvation free energy for water (FH2O)(FH2O) and fraction of areas of molecular shadow in the XY and ZX planes over area of enclosing rectangle (Sxyf and Sxzf) with r ranges 0.870–0.904. The best model was obtained from RSA model having r = 0.940 with good predictive ability (predicted compounds in training set and test set within ±1.0 unit of pIC50) and can be used in designing better selective COX-2 inhibitors among the congeners in future.

Graphical abstractQuantitative structure–activity relationship analysis was performed on a series of 1,3-diaryl-4,5,6,7-tetrahydro-2H-isoindole for their cyclooxygenase-2 (COX-2) inhibition. QSAR investigations were based on Hansch's extra thermodynamic multi-parameter approach and receptor surface analysis (RSA). QSAR investigations revealed that steric and electrostatic interactions are primarily responsible for COX-2 enzyme–ligand interaction.Figure optionsDownload full-size imageDownload as PowerPoint slide