MOLECULAR DOCKING, SYNTHESIS AND ANTI-INFLAMMATORY ACTIVITY OF SOME TETRASUBSTITUTED THIOPHENE DERIVATIVES

Abstract

A series of novel 4-amino-5-(4-oxo-3-aryl-3,4-dihydroquinazolin-2-yl)-2 (arylamino)thiophene-3-carbonitrile (7a-7j) were synthesized, characterized and evaluated for anti-inflammatory activity. Compounds 7e and 7h show % protection 45.34 % and 47.25 % respectively against carrageenan induced rat paw edema model whereas diclofenac sodium show 60.60 % after 4 hour at dose 20mg/kg. 7a, 7b, 7c, 7d, 7f, 7g, 7i and 7j show mild to moderate anti-inflammatory activity. Molecular docking experiments were carried on COX2 enzyme (pdb code: 1CX2) to identify potential COX2 inhibitor. The results indicate that 7a show lowest binding energy -9.32 kcal/mol with hydrogen bond interaction with ARG 120 and PRO 84 in comparison with reference compound SC 558 having binding energy -7.49 kcal/mol. Compounds 7e, 7g and 7h were found to have minimum binding energy -8.34, -

9.59 and -7.79 kcal/mol respectively. The docking results revealed that compound has good affinity with COX2 binding site.