a Department of Pharmacy , The University of Sydney , New South Wales , Australia.
Redox Rep. 1997 Feb;3(1):41-7. doi: 10.1080/13510002.1997.11747089.
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.
研究了一些目前处方的非甾体抗炎药（NSAIDs）（舒林酸、双氯芬酸、吡罗昔康、萘普生、布洛芬、吲哚美辛和阿司匹林）的自由基反应性，方法是观察它们在水溶液中热分解过硫酸钾引发丙烯酰胺自由基聚合反应中的作用，在 pH 7 和 50°C。聚合反应动力学分析表明，舒林酸、双氯芬酸、吡罗昔康、吲哚美辛和阿司匹林直接与碳中心聚丙酰胺自由基反应，从而减缓聚合反应。在 pH 7、离子强度 0.1 M 和 50°C 下，舒林酸、双氯芬酸、吡罗昔康、吲哚美辛和阿司匹林与聚丙酰胺自由基的反应的特定速率常数分别为 6850、262、76、30 和 21 M(-1) s(-1)。反应机制被假设为涉及药物的还原。另一方面，萘普生和布洛芬能够与引发的 SO4(•-)自由基反应，导致聚合抑制和药物氧化。这项研究验证了 NSAIDs 作为自由基清除剂的能力，并有可能在生物系统的“氧化应激”中作为链断裂剂参与。其中，舒林酸在与碳中心自由基相互作用时最具选择性和有效性，这可能反映了舒林酸在体内迅速还原为其活性硫代代谢物。
