2. Academic Validation
  3. Design, synthesis and biological evaluation of novel diarylacylhydrazones derivatives for the efficient treatment of idiopathic pulmonary fibrosis

Design, synthesis and biological evaluation of novel diarylacylhydrazones derivatives for the efficient treatment of idiopathic pulmonary fibrosis

  • Eur J Med Chem. 2023 Jan 5;245(Pt 2):114918. doi: 10.1016/j.ejmech.2022.114918.
Xingping Su 1,  Zui Tan 1,  Guan Wang 2,  Zhihao Liu 1,  Cailing Gan 1,  Lin Yue 1,  Hongyao Liu 1,  Yuting Xie 1,  Yuqin Yao 3,  Tinghong Ye 4
Affiliations

Affiliations

  • 1 Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • 2 Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China; Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • 3 West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
  • 4 Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. Electronic address: yeth1309@scu.edu.cn.
PMID: 36401884 DOI: 10.1016/j.ejmech.2022.114918
Abstract

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized with high mortality, unknown etiology, and lack of effective treatment. Many evidences validate that inhibiting the activation of STAT3 is an attractive therapeutic strategy for IPF. Herein, based on our previous findings that nifuroxazide (NIF) could effectively attenuate pulmonary fibrosis by inhibiting STAT3 activation, a series of diarylacylhydrazones derivatives have been designed and synthesized. Among them, compounds 44 and 52 could inhibit TGF-β1-induced abnormal activation of NIH-3T3 and A549 cells, as well as migration and EMT of A549 cells. In a bleomycin-induced mouse pulmonary fibrosis model, the oral administration of 44 and 52 (bioavailability F = 31.75% and 42.08%) improved mouse lung function and slowed the progression of IPF. Moreover, 52 could reverse the pulmonary fibrosis in treatment model. Collectively, this work shows 44 and 52 could be a potential lead compound for the treatment of IPF, and it is worthy of further study.

Keywords

Diarylacylhydrazones; Epithelial-mesenchymal transition; Idiopathic pulmonary fibrosis; Immune microenvironment; Nifuroxazide; STAT3.

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