Azamacrocycle Complexes: Synthesis and Xanthine Oxidase and Antioxidant Activity

Aims: Gout is caused by high uric acid in the blood that leads to excess uric acid crystallizing in the joints causing swelling and pain. Uric acid is produced from the breakdown of the purine which is released when cells die or introduced from the food we eat. The enzyme that helps in breakdown of purine to uric acid is xanthine oxidase (XO). Since XO makes the conversion of purine into uric acid happen, preventing its activity results to slow down of uric acid production. Such is the role of xanthine oxidase inhibitors (XOI). In this context we aimed to synthesize new complex which can be potent towards XOI and antioxidant properties.

Study Design: Based on the literature we have designed azamacrocyclic complexes for advanced biological applications.

Place and Duration of Study: Department of Chemistry, Research Laboratory, Yuvaraj’s College, University of Mysore, Mysore for synthesis and for biological activities Mahajana Life Science Research Laboratory, Department of Biotechnology, Microbiology and Biochemistry. June 2012-may 2013.

Methodology: The macrocyclic metal complexes were synthesized by the template condensation of diamine and formaldehyde in MeOH. After stirring for 10 min a solution of 1, 4-diaminobutane, metallic salt and 2, 4-pentanedione in MeOH was added and the resulting mixture was refluxed.

Results: Macrocylic metal complexes containing phenylene bridges have been synthesized and subjected to biological activities. Among the four synthesized complexes (3a-3d), 3d exhibited 83.2% of XO inhibition and also showed potent antioxidant activity. The same was also evident from structure activity relationship with atomic contact energy values of -285.78 compared to allopurinol with -200.02.

Conclusion: From the present study, we infer that, aza macrocyclic metal complexes could lead to the development of newer therapeutics for gout and other inflammatory diseases which are caused by oxidative stress.