Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives

A series of sixteen ring-substituted N-arylcinnamanilides, previously described as highly antimicrobially effective against a wide spectrum of bacteria and fungi, together with two new derivatives from this group were prepared and characterized. Moreover, the molecular structure of (2E)-N-(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide as a model compound was determined using single-crystal X-ray analysis. All the compounds were tested for their anti-inflammatory potential, and most tested compounds significantly attenuated the lipopolysaccharide-induced NF-kappa B activation and were more potent than the parental cinnamic acid. (2E)-N-[2-Chloro-5-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide, (2E)-N-(2,6-dibromophenyl)-3-phenylprop-2-enamide, and (2E)-N-(2,5-dichlorophenyl)-3-phenylprop-2-enamide demonstrated the highest inhibition effect on transcription factor NF-kappa B at the concentration of 2 mu M and showed a similar effectiveness as the reference drug prednisone. Several compounds also decreased the level of TNF-alpha. Nevertheless, subsequent tests showed that the investigated compounds affect neither I kappa B alpha level nor MAPKs activity, which suggests that the N-arylcinnamanilides may have a different mode of action to prednisone. The modification of the C-(2,C-5)' or C-(2,C-6)' positions of the anilide core by rather lipophilic and bulky moieties seems to be preferable for the anti-inflammatory potential of these compounds.