QSAR Analysis of 2,3‐Diaryl Benzopyrans/Pyrans as Selective COX‐2 Inhibitors Based on Semiempirical AM1 Calculations

Abstract

AbstractQuantitative structure‐activity relationship (QSAR) analysis was performed on a combined series of 2,3 diaryl benzopyrans and pyrans for their cyclooxygenase‐2 (COX‐2) inhibition. QSAR investigations based on semiempirical, Austin Model‐1 (AM1) calculations reveal that electronic and hydophobic interactions are primarily responsible for COX‐2 enzyme‐ligand interaction. The derived QSAR model aided by residual analysis demonstrated that the COX‐2 inhibitory activity is highly correlated with the electronic descriptors, lowest unoccupied molecular orbital (ELUMO), Dipole‐Z and hydrophobicity of the molecules. The conclusion can be drawn that more hydrophobic, electron‐withdrawing substituents at 3rd aromatic ring of the lead structure improves activity. The lesser the Z component the ligand has, the more correct its orientation towards the COX‐2 binding site. The derived QSAR model shows good internal (exemplified through leave one out‐q2=0.786) and external (r$\rm{ {_{pred}^{2}}}$=0.5737) predictive ability for a test set and can be used in designing better selective COX‐2 inhibitors among these congeners in future.