Original articleSchiff base transition metal complexes as novel inhibitors of xanthine oxidase
Graphical abstract
Introduction
Schiff base transition metal complexes have been of great interest for many years since they are becoming increasingly important as biochemical, analytical and antimicrobial reagents [1]. Many Schiff base transition metal complexes are reported to have anticancer and antimicrobial activities [2], [3], [4]. It was reported that some drugs have greater activity when administered as metal complexes than that as free organic compounds [5]. So, Schiff base transition metal complexes may be an untapped reservoir for drugs.
Xanthine oxidase (XO) (EC 1.1.3.22) catalyzes the hydroxylation of hypoxanthine and xanthine to yield uric acid and superoxide anions. The enzyme is responsible for the medical condition known as gout which is caused by the deposition of uric acid in the joints leading to painful inflammation. On the other hand, superoxide anions formed by the enzyme has been linked to postischaemic tissue injury and oedema [6] as well as to vascular permeability [7]. XO can also oxidize synthetic purine drugs, such as antileukaemic 6-mercaptopurine, with loss of their pharmacological properties [8]. Then, the control of the action of XO may help the therapy of some diseases. Allopurinol, a potent inhibitor of XO has been used for the therapy of gout for a long time [9]. However, considering its side effects and its inability to prevent the formation of free radicals by the enzyme [10], the screening of new XO inhibitors is required.
As a follow-up to our previous characterization of a Schiff base zinc(II) complex as XO inhibitor [11], 20 Schiff base transition metal complexes were evaluated for their inhibitory activities against XO, of which 11 were newly synthesized. The results showed that the Schiff base metal complexes could be the potential selective XO inhibitors. The structure–activity relationship was discussed.
Section snippets
Chemistry
Eleven transition metal complexes (1–11) derived from Schiff bases were obtained from cheap, eco-friendly and commercially affordable reagents. Complexes 1–7 were synthesized under the solvolthermal conditions. Complexes 8–11 were synthesized through the traditional synthetic procedures at room temperature.
Structure description of the complexes
Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7, Fig. 8, Fig. 9, Fig. 10, Fig. 11 are the thermal ellipsoid plots of the complexes 1–11 together with the atomic labeling systems. The complexes from 1 to 7 are structurally similar trinuclear compounds. Each complex consists of two M1L units (M1 = Ni for 1 and 7, Mn for 2, 4 and 5, Co for 3 and 6; L = SALPD for 1, 2 and 3, NAPTPD for 4, 5 and 6) connected to each other by a completely encapsulated third metal ion M2 (M2 = Ni for 1 and 7, Mn for 2
Conclusion
Twenty Schiff base transition metal complexes were evaluated for their effect on XO, of which 11 were newly synthesized and characterized by X-ray diffraction. Most of the complexes showed potent inhibitory activity against XO, of which the cadmium(II) complex (8) was the best. The metal ions and ligands were all important for the inhibitory activities against the enzyme. The XO inhibition of the Schiff base metal complexes most probably result from their direct interactions with XO “in the
Chemistry
All chemicals (reagent grade) used were commercially available. Elemental analyses for C, H and N were performed on a Perkin–Elmer 240C elemental analyzer. Complexes 12–20 were synthesized according to the literatures (12: an acetate-bridged trinuclear copper(II) complex derived from N,N′-bis(salicylidene)-1,3-propanediamine; 18: a nitrate salt of trinuclear zinc(II) complex derived from N,N′-bis(salicylidene)-1,3-propanediamine [14]; 13: an azide bridged one-dimensional manganese(II) complex
Acknowledgments
The work was financed by grant (Project 30672516) from National Natural Science Foundation of China.
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