Background: NSAIDs are the most widely prescribed medications worldwide for their anti-inflammatory, antipyretic, and analgesic effects However, their chronic use can lead to several adverse drug events including GI toxicity. The selective COX-2 inhibitors developed as gastro-sparing NSAIDs also suffer from serious adverse effects which limit their efficacy.
Objective: Local generation of reactive oxygen species is implicated in NSAID-mediated gastric ulceration and their combination with H2 antagonists like famotidine reduces the risk of ulcers. The objective of this work was to design and synthesize
novel methanesulphonamido isoxazole derivatives by hybridizing the structural features of NSAIDs with those of antiulcer
drugs (ranitidine, famotidine, etc.) to utilize a dual combination of anti-inflammatory activity and reducing (antioxidant) potential.
Method: The designing process utilized three dimensional similarity studies and utilized an isoxazole core having a potential for anti-inflammatory as well as radical scavenging antioxidant activity. The compounds were assayed for their antiinflammatory activity in established in vivo models. The in vitro antioxidant activity was assessed in potassium ferricyanide
reducing power (PFRAP) assay employing ascorbic acid as the standard drug. Results: Compounds (5, 6, 9 and 10) showed
anti-inflammatory activity comparable to the standard drugs and were also found to be non-ulcerogenic at the test doses.
Compounds 6-10 exhibited good antioxidant effect in the concentration range of 1.0-50.0 µmol/ml. The test compounds
were also found to comply with the Lipinski rule suggesting good oral absorption.
Conclusion: A new series of isoxazole based compounds is being reported with good anti-inflammatory activity coupled
with antioxidant potential as gastro-sparing anti-inflammatory agents.