Antioxidant activity of NSAID hydroxamic acids

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Biochemistry

Background:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain and inflammation.
• Hydroxamic acid derivatives offer potential for enhanced therapeutic properties.
• Investigating antioxidant and metal chelating activities of NSAID derivatives is crucial for drug development.

Purpose of the Study:

• To synthesize and evaluate antioxidant, radical scavenging, and metal chelating activities of seven hydroxamic acid derivatives of NSAIDs.
• To identify the most potent derivative for these activities.
• To explore potential mechanisms underlying the observed activities.

Main Methods:

• Synthesis of seven hydroxamic acid derivatives from NSAIDs (ibuprofen, fenoprofen, ketoprofen, indomethacin, diclofenac).
• Assay of antioxidant activity (ANT) and radical scavenging activity (EC50).
• Measurement of metal chelating activity (EC50) for iron.

Main Results:

• All seven derivatives exhibited significant antioxidant, radical scavenging, and metal chelating activities.
• N-methylhydroxamic acid of diclofenac demonstrated the highest antioxidant (ANT=88.0%) and radical scavenging (EC50=60.1 microg mL-1) efficacy, comparable to butylated hydroxyanisole.
• Ibuproxam showed the strongest iron chelating ability (EC50=255.6 microg mL-1) among the derivatives, though weaker than EDTA.

Conclusions:

• Hydroxamic acid derivatives of NSAIDs possess significant antioxidant and radical scavenging properties, potentially linked to electron conjugation.
• Metal chelating activity appears to involve a different mechanism, favoring more hydrophilic compounds.
• These findings suggest potential for developing novel NSAID-based therapeutics with enhanced antioxidant and chelating functionalities.