DESIGN, SYNTHESIS, MOLECULAR DOCKING AND BIOLOGICAL EVALUATION OF SOME NOVEL QUINAZOLIN-4(3H)-ONE DERIVATIVES AS ANTI-INFLAMMATORY AGENTS

Abstract

In view of their expected anti-inflammatory activity, novel series of 6-iodo-2-phenyl-quinazolin-4(3H)-one (4-12a-d) were designed and synthesized in order to evaluate their anti-inflammatory activity using carrageenan-induced rat paw edema assay. Most of the novel quinazolinone derivatives showed considerable potent anti-inflammatory activities of superior G.I.T. safety profile in experimental rats in comparing to indomethacin as a reference drug. The molecular docking was performed for all synthesized compounds to assess their binding affinity to COX-2 enzyme in order to rationalize their anti-inflammatory activity in a qualitative way. The obtained data from the molecular modeling was strongly correlated with that obtained from the biological screening. The highest binding affinities were noticed for compounds 8a, 12b and 10b which showed the highest anti-inflammatory activities of this series. Compounds 12b, 9c and 8a exhibited the least ulcerogenic effect in all of the experimental animals.