Involvement of electron and hydrogen transfers through redox metabolism on activity and toxicity of the nimesulide.

An electronic study of nimesulide was performed by using density functional theory calculations. The activities of the six different derivatives were related with electron donating or accepting capacities. All compounds which had nitro moiety had low electron donating and high electron accepting capacities. However, the reduced derivative of nimesulide have more electron donating capacity than other compounds. The highest spin density contribution in nitro and lowest spin density contribution on phenoxyl moieties can be related with preferential metabolism by reduction when compared with the oxidation. The redox behavior between nitro and amino groups can be related with anti-inflammatory mechanism of nimesulide. These results explain the redox influence of nitro moiety on biological metabolism and mechanism of nimesulide.