Reactions of non-steroidal anti-inflammatory drugs with polyacrylamide free radicals

Summary

The free radical reactivity of a number of currently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) (sulindac, diflunisal, piroxicam, naproxen, ibuprofen, indomethacin and aspirin) was studied by observing their action on the free radical polymerization of acrylamide initiated by the thermal decomposition of potassium peroxodisulfate in aqueous solution at pH 7 and 50°C. Analysis of the kinetics of the polymerization reaction showed that sulindac, diflunisal, piroxicam, indomethacin and aspirin reacted directly with the carbon-centred polyacrylamide free radicals, thereby retarding the polymerization. The specific rate constants for reaction of sulindac, diflunisal, piroxicam, indomethacin and aspirin with polyacrylamide radicals at pH 7, ionic strength 0.1 M and 50°C were found to be 6850, 262, 76, 30 and 21 M⁻¹ s⁻¹ respectively. The reaction mechanism is postulated to involve reduction of the drug. On the other hand, naproxen and ibuprofen were able to react with the initiating SO₄^•- radicals, causing inhibition of the polymerization and oxidation of the drug. This study verifies the ability of NSAIDs to react as free radical scavengers and potentially to participate as a chain breaking agent in ‘oxidative stress’ in biological systems. Among them, sulindac is the most selective and effective when interacting with the carbon-centred radicals, and this may be a reflection of the rapid reduction in vivo of sulindac to its active sulphide metabolite.