Manganese-mefenamic acid complexes exhibit high lipoxygenase inhibitory activity

Area of Science:

• Coordination chemistry
• Medicinal chemistry
• Pharmacology

Background:

• Metal coordination can enhance non-steroidal anti-inflammatory drug (NSAID) efficacy.
• The mechanisms and effects of many metal-NSAID complexes remain poorly understood.

Purpose of the Study:

• To synthesize and characterize manganese-mefenamic acid (Mn-mef) complexes.
• To investigate the pharmaceutical effects, including enzyme inhibition and antioxidant activity, of these complexes.
• To explore the structure-activity relationship between Mn-mef complexes and their biological targets.

Main Methods:

• Synthesis and structural characterization of three manganese-mefenamic acid complexes.
• In vitro evaluation of lipoxygenase (LOX-1) inhibitory activity.
• Computer docking studies to predict binding modes with LOX-1.
• Assessment of antioxidant activity.

Main Results:

• The synthesized Mn-mef complexes demonstrated significantly higher LOX-1 inhibitory activity than mefenamic acid.
• Complex spatial arrangements influenced the inhibitory mechanism, with smaller complexes binding competitively and larger ones un-competitively.
• Mn-mef complexes exhibited superior antioxidant activity compared to the parent ligand, attributed to the manganese center.
• Computer docking validated the experimental findings on enzyme-ligand interactions.

Conclusions:

• Mn-mef complexes enhance the anti-inflammatory potential of mefenamic acid through altered enzyme interaction modes and improved antioxidant capacity.
• Metal-NSAID complexes, owing to unique spatial configurations, can achieve more specific and efficient interactions with target enzymes.
• This study provides evidence for the superior therapeutic potential of metal-NSAID complexes over conventional NSAIDs.