Synthesis of furoxan derivatives of diclofenac as potent anti-inflammatory agents with reduced GI toxicity

A new series of NO donating furoxan derivatives of diclofenac have been synthesized by linking diclofenac to selected furoxan moieties and have been investigated for their anti-inflammatory, analgesic, ulcerogenic, lipid peroxidation, hepatotoxicity, histopathological and NO releasing properties. All the hybrid derivatives are endowed with anti-inflammatory activity comparable to diclofenac but unlike this drug they show reduced GI toxicity. The compounds 4-[(2-(2-(2-(2,6-dichlorophenylamino)phenyl)acetamido)ethoxy)carbonyl]-3-methyl furoxan 12 having amide-ester linkage and 4-[(2-(2-(2,6-dichlorophenylamino)phenyl)acetoxy)methyl]1-3-methyl-furoxan 13a having ester linkage show greater anti-inflammatory activity comparable to standard drug diclofenac. These compounds 12 and 13a also show higher gastrointestinal protection in comparison to standard drug diclofenac.