3D QSAR ANALYSIS OF SOME HETEROCYCLIC COMPOUNDS AS CYCLOOXYGENASE-2 INHIBITORS

Abstract

The 3D-QSAR studies have been carried out on a set of 19 compounds using APEX-3D expert system for identification of essential structural and physicochemical requirements in terms of common biophoric sites and secondary sites for binding and interacting with cyclooxygenase-2 enzyme. Among several models, one model has been identified with the statistical criteria r≥0.9, chance<0.02, superimposition match>0.67. The model with three common biophoric sites such as center of triazole ring for A, center of phenyl ring for B, and charge heteroatom for C. In addition to these biophoric sites, three secondary sites for all 19 compounds indicated that total hydrophobicity at SSa, hydrogen acceptor at SSc contribute positively, whereas, hydrogen acceptor at SSb contributes negatively for the cyclooxygenase-2 inhibitory activity. Statistically significant correlation (r>0.905) was obtained between the physicochemical parameters and biological activity. These studies may be useful in designing molecules with better cyclooxygenase-2 inhibitory activity.