title: Synthesis and biological evaluation of 4-oxoquinoline-3-carboxamides derivatives as potent anti-fibrosis agents.
abstract: Thirty-one 4-oxoquinoline-3-carboxamides derivatives were synthesized and evaluated for their anti-fibrotic activities by the inhibition of TGF-β1-induced total collagen accumulation and anti-inflammatory activities by the inhibition of LPS-stimulated TNF-α production. Among them, three compounds (10a, 10l and 11g) exhibited potent inhibitory effects on both TGF-β1-induced total collagen accumulation and LPS-stimulated TNF-α production. Furthermore, oral administrations of 10l at a dose of 20 mg/kg/day for 4 weeks effectively alleviated lung inflammation and injury, and decreased lung collagen accumulation in bleomycin-induced pulmonary fibrosis model. Histopathological evaluation of lung tissue confirmed 10l as a potential, orally active agent for the treatment of pulmonary fibrosis.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Jiqiang
authors.initials: J
authors.lastname: He
authors.affiliation: College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, PR China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Pu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Cao
authors.affiliation: College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, PR China.
authors.forename: Yuzhe
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China. Electronic address: chenlijuan125@163.com.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D042462:4-Quinolones / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001761:Bleomycin / Q000633:toxicity; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D042462:4-Quinolones; D000893:Anti-Inflammatory Agents; D000903:Antibiotics, Antineoplastic; D008070:Lipopolysaccharides; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D003094:Collagen
keywords: 4-Oxoquinoline-3-carboxamides; Anti-inflammatory; Collagen accumulation; Pulmonary fibrosis; TGF-β1; TNF-α