QSAR Investigations on Benzylideneamino and Phenyliminomethyl Scaffolds for Selective COX-2 Inhibition: A Hansch Approach

E.      Manivannan; S.   C.   Chaturvedi

Abstract

Cyclooxygenase inhibitory and selectivity profile of a combined series of thirty one aryl sulphonamide compounds possessing 4-benzylideneamino or 4-phenyliminomethyl scaffolds were subjected to QSAR study using Hansch approach. The compounds in the selected series were characterized using classical aromatic substituent constants like hydrophobicity (p), molar refractivity (MR), Hammett electronic (s), electronic field effect (F), resonance effect (R), and some indicator variables encoding molecular group contributions. Statistically significant QSAR models were generated using multiple regression analysis and cross-validation tools. The derived QSAR models demonstrated that the COX-2 selectivity over COX-1 is predominantly influenced by the central core – N=C- of the diaryl system. Further, the study also indicated that the electronic properties and structural variation in the para position of the phenyl ring (B) governs the COX-2 selectivity of the title compounds. The derived results reveal the important structural features significant for improved COX-2 inhibitory activity and selectivity of these novel aryl sulfonamides.

Keywords: QSAR, COX-1, COX-2, Selectivity, NSAIDs, 4-benzylideneamino, 4-phenyliminomethyl, Aryl sulfonamide