Synthesis, Characterization, and Antibacterial Activity of Novel Mutual Non-Steroidal Anti-inflammatory Prodrugs

Abstract

Non steroidal anti-inflammatory drugs (NSAIDs) are among the most used analgesic and anti-inflammatory drugs. However inhibition of cyclooxygenase1 and acidic groups such as carboxylic groups in most NSAIDs cause gastrointestinal (GI) side effects. Therefore masking the acidic groups till it pass through the GI tract will decrease the direct GI side effects and because N-(2,6-dimethylphenyl)-acetamide 1 also has anti-inflammatory activity so the synthesized ester prodrugs might act as mutual prodrugs. Moreover, because of emerging of new strains of bacteria and resistance of bacteria to the available antibacterial agents, new antibacterial agents are needed. The NSAIDs have antibacterial activity and N-(2,6-dimethylphenyl) acetamide 1 also has antibacterial activity so binding of these molecules with each other might give more potent antibacterial agent. 2-Chloro-N-(2,6dimethyl phenyl) acetamide 1 was utilized to synthesize ester prodrug of various NSAIDs 2a-f. The 2-Chloro-N-(2,6dimethylphenyl)-acetamide 1 undergo substitution reaction at α position with various sodium carboxylate of NSAIDs 2a-f in DMSO. The constitution of the newly synthesized ester prodrugs of NSAIDs 3a-f had been confirmed on the basis of their IR, ¹H and ¹³C-NMR spectral data. All the synthesized ester prodrugs 3a-f were screened for their in vitro antibacterial activities against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 however, their antibacterial activity decreased compared with their starting 1 and 2a-f.