Synthesis and biological evaluation of the pirfenidone derivatives as antifibrotic agents.

A total of 24 pirfenidone derivatives were designed, synthesized and evaluated for their inhibitory activity against the human lung fibroblast cell line MRC-5. These compounds showed the remarkable proliferation inhibition against MRC-5 compared to pirfenidone as the positive control. The possible mechanism of this kind of derivatives as antifibrotic agents was explored. The molecular docking and p38 binding affinity assays demonstrated that the antifibrotic potential of the pirfenidone derivatives was possibly through the inhibition of p38 MAPK signaling pathway. The data from this study suggested that p38 might be a potential therapeutic target for the new generation antifibrotics. All the pirfenidone derivatives are reported here for the first time.