Manganese-mefenamic acid complexes exhibit high lipoxygenase inhibitory activityElectronic supplementary information (ESI) available: The line weaver-Burk plot for the inhibition of LOX-1 by complexes 1-3; the docking area in this work, and the spatial environment of the complex 1 docked inside the cavity IIa of LOX-1; DPPH radical scavenging by the complexes 1-3; the SOD inhibitory activity, and the selected IR data for the complexes 1-3. CCDC 931669, 931670 and 955463. For ESI and crystallogra

The coordination of non-steroidal anti-inflammatory drugs (NSAIDs) to metal ions could improve the pharmaceutical efficacy of NSAIDs due to the unique characteristics of metal complexes. However, the structures of many metal-NSAID complexes are not well characterized; the functional mechanism and pharmaceutical effect of these complexes thus are not fully understood. In this work, three manganese-mefenamic acid (Mn-mef) complexes were synthesized and structurally characterized, and their pharmaceutical effect was investigated. We found that the three Mn-mef complexes exhibit higher lipoxygenase (LOX-1) inhibitory activity (IC 50 values are 16.79, 38.63 and 28.06 μM, respectively) than the parent ligand mefenamic acid (78.67 μM). More importantly, the high inhibitory activity of the Mn-mef complexes is closely related to their spatial arrangements, which determine their interaction with LOX-1. Computer docking of the Mn-mef complexes with the LOX-1 confirms the experimental results: smaller Mn-mef complexes tend to bind competitively to LOX-1 at the substrate binding site, which is also analogous to the binding of the ligand mefenamic acid, while the bulky metal complexes inhibit the enzyme activity un-competitively. In addition, the Mn-mef complexes exhibit higher anti-oxidant activity than the ligand mefenamic acid. The higher anti-oxidant activity of the Mn-mef complexes apparently originated from the manganese centre of the complexes. We thus conclude that Mn-mef complexes enhance the anti-inflammatory activity of mefenamic acid by increasing their activity via changing their interaction mode with the enzymes, and/or by improving their anti-oxidant ability using metal ions. This work provides experimental evidence that with the unique spatial arrangements, metal-NSAID complexes could interact with the target enzymes more specifically and efficiently, which is superior to their parent NSAID ligand. The coordination of non-steroidal anti-inflammatory drugs (NSAIDs) to metal ions could improve the pharmaceutical efficacy of NSAIDs due to the unique characteristics of metal complexes.