QSAR STUDY OF 4-BENZYLIDENEAMINO-BENZENESULFONAMIDES AS SELECTIVE COX-2 INHIBITORS

Jain Amit¹*, Singh Asheesh², Barjatya Pooja¹, Gokhale Prasad³

Ipca Laboratories Ltd; Sejavta; Ratlam (MP) India

ABSTRACT

A QSAR study on 4-benzylideneamino-benzenesulfonamide derivatives as selective cyclooxygenase-2 (COX-2) inhibitors was performed with 21 (16 training + 5 test) compounds. Molecular modeling studies were performed using Chemoffice 6.0 supplied by cambridgesoft. The regression analysis was carried out using a computer program called VALSTAT. The substitution Different monosubstituents preferably at the 3- or 4-position of the phenyl ring had the greatest influence on COX-2 selectivity. Replacement of the 4-hydroxy moiety with an electron withdrawing group such as 4-fluoro, 4-methoxycarbonyl, or 4-nitro substituents increased COX-2 inhibitory potency and selectivity. However, 3-nitro substituent resulted in loss of COX-2 inhibitory potency. On the other hand, the 4-N, N-dimethylamino substituent exhibited potent and selective inhibition of COX-2. Among these compounds with monosubstituted at the para-position, the COX-2 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 & validated r2 (q2) =0.671. This study can help in rational drug design of new cyclooxygenase-2 inhibitor with predetermined affinity.

Keywords: QSAR analysis, 4-benzylideneamino, 4-phenyliminomethyl-benzenesulfonamide, cyclooxygenase-2.