Synthesis, Characterization and Anti-Inflammatory Activity of Metal Complexes of 5-Methyl-N-[4-(Trifluoromethyl) Phenyl]-Isoxazole-4-Carboxamide on Carrageenan Induced Arthritic Rats

Leflunomide, a type of disease modifying antirheumatic drug (DMARD) is a pyrimidine synthesis inhibitor which is chemically and pharmacologically very heterogeneous. It was selected as a bioactive ligand to react with hydrated salts of essential and trace metals to afford [M(Lef)4]X2, type complexes which were characterized by FT-IR, 1H-NMR and elemental analysis. In these reactions leflunomide acted as monodentate ligand coordinated to metal ions through a cyanide group. The antiinflammatory activity of leflunomide and synthesized metal complexes were examined in carrageenan induced arthritic rats at two different doses i.e. 5 mg Kg-1 and 7.5 mg Kg-1. Leflunomide showed 99.56±0.19 and 99.81±0.71 % edema inhibition at above mentioned doses, while in all leflunomidemetal complexes, the carrageenan induced anti-inflammatory activity of leflunomide decreased significantly (p< 0.005) indicating that metals affected leflunomide activity on complexation. These changes are in dose response relationship. Maximum retention of leflunomide anti-inflammatory activity was observed in leflunomide-manganese complex. Results also indicated dose response relationship as leflunomide metal complexes of manganese, ferrous, ferric, copper and nickel showed reasonable retention of anti-inflammatory activity at 5mg Kg-1 but their activity reduced markedly at 7.5mg Kg-1. In metal complex of calcium, chromium, cobalt and zinc anti-inflammatory activity increased as the dose increased.