Koncic Marijana Zovko, Rajic Zrinka, Petric Neva, Zorc Branka
Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
Acta Pharm. 2009 Jun;59(2):235-42. doi: 10.2478/v10007-009-0017-8.
In the present study, seven hydroxamic acid derivatives of nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, fenoprofen, ketoprofen, indomethacin and diclofenac) were found to possess significant antioxidant, radical scavenging and metal chelating activities. The most active antioxidant and radical scavenger was N-methylhydroxamic acid of diclofenac (ANT = 88.0% and EC50 = 60.1 microg mL-1). The activity of the standard substance, butylated hydroxyanisole, in the two assays was ANT = 86.9% and EC50 = 18.8 microg mL-1, respectively. Ibuproxam was the strongest iron chelator among investigated hydroxamic acids (EC50 = 255.6 microg mL-1), yet significantly weaker than the standard substance, EDTA (EC50 = 29.1 microg mL-1). It seems that different mechanism is involved in metal chelating activity than in antioxidant and radical scavenging activity. Antioxidant and radical scavenging activities may be connected with conjugation of the nitrogen lone electron pair with the carbonyl group. On the other hand, more hydrophilic substances tend to be better iron chelators.
在本研究中，发现七种非甾体抗炎药（NSAIDs）（布洛芬、非诺洛芬、酮洛芬、吲哚美辛和双氯芬酸）的异羟肟酸衍生物具有显著的抗氧化、自由基清除和金属螯合活性。活性最强的抗氧化剂和自由基清除剂是双氯芬酸的N-甲基异羟肟酸（ANT = 88.0%，EC50 = 60.1 μg mL-1）。标准物质丁基羟基茴香醚在这两种测定中的活性分别为ANT = 86.9%和EC50 = 18.8 μg mL-1。在研究的异羟肟酸中，异丁普生是最强的铁螯合剂（EC50 = 255.6 μg mL-1），但明显弱于标准物质乙二胺四乙酸（EDTA）（EC50 = 29.1 μg mL-1）。金属螯合活性似乎与抗氧化和自由基清除活性涉及不同的机制。抗氧化和自由基清除活性可能与氮孤对电子与羰基的共轭有关。另一方面，亲水性更强的物质往往是更好的铁螯合剂。
