title: Synthesis and biological evaluation of the pirfenidone derivatives as antifibrotic agents.
abstract: 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.
authors: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors: Zhen
authors: Z
authors: Ma
authors: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors: Youlu
authors: Y
authors: Pan
authors: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors: Wenhai
authors: W
authors: Huang
authors: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors: Yewei
authors: Y
authors: Yang
authors: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors: Zunyuan
authors: Z
authors: Wang
authors: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors: Qin
authors: Q
authors: Li
authors: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors: Yin
authors: Y
authors: Zhao
authors: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors: Xinyue
authors: X
authors: Zhang
authors: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China. Electronic address: shenzr601@163.com.
authors: Zhengrong
authors: Z
authors: Shen
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis / Q000517:prevention & control*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D011728:Pyridones; C093844:pirfenidone; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Antifibrotic; Derivatives; IPF; Pirfenidone; p38