Title:Design and Synthesis of Novel Anti-inflammatory/Anti-ulcer Hybrid Molecules with Antioxidant Activity
Volume: 17
Issue: 9
Author(s): Bhim Bahadur Chaudhari, Alka Bali*Ajitesh Balaini
Affiliation:
- University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, 160014,India
Keywords:
Anti-inflammatory activity, isoxazole, carrageenan-induced paw edema, NSAIDs, non-ulcerogenic, hybrid.
Abstract:
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 gastrosparing
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.
Methods: 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 anti-inflammatory 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 antiinflammatory
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 antiinflammatory
activity coupled with antioxidant potential as gastro-sparing anti-inflammatory agents.
