Synthesis, Characterization And Activity Of Mn(Ⅱ) Complexes Of Mefenamic Acid

Metal complexes of Non-sterodial anti-inflammatory drugs(NSAIDs) have attracted much interest due to their unique biological functions. Metal-NSAIDs can enhance anti-inflammatory activity and reduce gastrointestinal toxicity compared with its uncomplexed parent drug. This work aims to synthesize manganese complexes with mefenamic acid, which is tradition cyclooxygenase inhibitor, as ligands. The structure, oxidation activity, radicals scavenge, and the inhibition of lipoxygenase activity were systematically investigated. The work laid the foundation for the future exporation of their potential applications as anti-inflammatory drugs.With different small molecules as co-liands, three manganese-mefenamic acid complexes have been synthesized:Mn(Mef)2(MeOH)4(1), Mn(Mef)2(Bipy)(MeOH)2(2), Mn(Mef)2(Phen)(MeOH)2(3). The structures of these compounds were characterized with X-ray single crystal diffraction, elemental analysis, UV-vis spectroscopy, Infrared spectroscopy. In all three complexes, manganese ions are coordinated by the oxygenatoms form two mefenamic acid ligands and four small molecules.The inhibition to 5-lipoxygenase activity of the three complexes was studied. All three complexes showed a good inhibitory activity, and the activity of the complexes l is much higher than that of 2 and 3. Comparing to l, the complexes 2 and 3 with small molecule ligands in terms of structure is relatively crowded around the manganese ions, thus their inhibitory is low. Interestingly, their inhibition mechanism is also different, for complex l, it is competitive inhibiton, while for complexes 2 and 3, they are noncompetitive inhibition. In addition, high temperature can significantly improve the inhibitory activity of all three complexes.The inhibitory activity of the manganese-mefenamic acid complexes could be possibily through oxidase inhibition, manganese-mefenamic acid complexes could affect the oxidation-reduction reation of 5-lipoxygenase. The different inhibitory activity of the complexes may be due to the different steric hindrance of manganese center.We found that manganese-mefenamic acid complexes exhibit excellent radical scavenging ability and SOD activity than the mefenamic acid. These results indicate the potential of the manganese-mefenamic acid complexes as anti-drugs.