Inhibition behavior on alkaline phosphatase activity, antibacterial and antioxidant activities of ternary methimazole–phenanthroline–copper(II) complex

Abstract

Methimazole (MeimzH), a sulfur containing compound, is an antithyroid drug commonly used to treat Graves’ disease acting as an inhibitor of the enzyme thyroid peroxidase. A new ternary [Cu(MeimzH)2 (phen)(H2O)2]Cl2 (Cu-Met-phen) complex of this drug containing also phenanthroline as a second ligand (phen) was synthesized and characterized by elemental analysis, dissolution behavior, thermogravimetric analysis, UV–Vis, diffuse reflectance, FTIR and EPR spectroscopies. As it is previously reported, the binary [Cu(MeimzH)2(H2O)2](NO3)2H2O (Cu-Met) complex can act as an inhibitor of alkaline phosphatase (ALP). In this work, the inhibitory effect of methimazole, phenanthroline, [Cu(phen)2Cl]Cl (Cu-phen) and the new ternary complex has also been investigated and compared with Cu-Met together with in vitro tests of susceptibility against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis bacteria. To our knowledge, the antibacterial activity of methimazole is determined for the first time. For the ternary complex, the results show that the coordination of the drug increased its antibacterial effect especially against E. faecalis demonstrating a strong effect against S. aureus and S. epidermidis. The assays also indicate that in same strains the new complex show better activity than their ligands. The ability for the inhibition of alkaline phosphatase (ALP) was lower than that of the binary complex (Cu-Met) probably due to the absence of labile ligands around the metal center. Moreover, the antioxidant activity of the complexes decreases as follows: CuMet > Cu-Phen > Cu-Met-Phen.