QSAR Study of 4-Benzylideneamino-Benzenesulfonamides and 4-Phenyliminomethyl-Benzenesulfonamides as Selective Cox-1 and Cox-2 Inhibitors

Abstract

A QSAR study on 4-benzylideneamino-benzenesulfonamide and 4-phenyliminomethyl-benzenesulfonamides derivatives as selective cyclooxygenase-2 (COX-2) and COX-1 inhibitors was performed with 21 (16 training + 5 test) compounds. Molecular modeling studies were performed using Chemoffice 6.0 supplied by cambridgesoft. The sketched structures were subjected to energy minimization and the lowest energy structure was used to calculate the physiochemical properties. The regression analysis was carried out using a computer program called VALSTAT. The best models were selected from the various statistically significant equations. The substitution Different monosubstituents preferably at the 3- or 4-position of the phenyl ring had the greatest influence on selectivity (COX-1 and COX-2). Replacement of the 4-hydroxy moiety with an electron withdrawing group such as 4-fluoro, 4-methoxycarbonyl, or 4-nitro substituents increased inhibitory potency and selectivity. However, 3-nitro substituent resulted in loss of inhibitory potency. On the other hand, the 4-N, N-dimethylamino substituent exhibited potent and selective inhibition of cyclooxygenase. Among these compounds with monosubstituted at the para-position, cyclooxygenase the inhibitory selectivity order was 4-F > 4-CO2Me > 4-NMe2 > 4-NO2 > 4-OH > unselective 3-NO2. The analysis resulted in QSAR equation, which suggests that, n=16, r=0.880, r2=0.774, adjusted squared multiple R=0.713, Standard error of estimate(s) = 0.106 and validated r2 (q2) =0.671. This study can help in rational drug design of new cyclooxygenase-2 inhibitor with predetermined affinity.