Antioxidant activity of NSAID hydroxamic acids

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 μg mL^-1). The activity of the standard substance, butylated hydroxyanisole, in the two assays was ANT = 86.9% and EC₅₀ = 18.8 μg mL^-1, respectively. Ibuproxam was the strongest iron chelator among investigated hydroxamic acids (EC₅₀ = 255.6 μg mL^-1), yet significantly weaker than the standard substance, EDTA (EC₅₀ = 29.1 μg 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.