Synthesis and biological evaluation of 4-oxoquinoline-3-carboxamides derivatives as potent anti-fibrosis agents

doi:10.1016/j.bmcl.2014.10.071

Bioorganic & Medicinal Chemistry Letters

Volume 24, Issue 24, 15 December 2014, Pages 5666-5670

https://doi.org/10.1016/j.bmcl.2014.10.071 Get rights and content

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.

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Acknowledgments

We greatly appreciated the financial support from China Postdoctoral Science Foundation (No. 2014M552373) and National Key R&D Programs of China (2012ZX09103101-017).

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Citation Excerpt :
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^†: These authors contributed equally.

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Synthesis and biological evaluation of 4-oxoquinoline-3-carboxamides derivatives as potent anti-fibrosis agents

Abstract

Graphical abstract

Section snippets

Acknowledgments

Biochem. Biophys. Res. Commun.

Mucosal Immunol.

Bioorg. Med. Chem. Lett.

Biochim. Biophys. Acta

Bioorg. Med. Chem. Lett.

Chest

Chest

Cytokine

Semin. Arthritis Rheum.

J. Cyst. Fibros.

Bioorg. Med. Chem.

Bioorg. Med. Chem.

Fitoterapia

Eur. J. Med. Chem.

Int. J. Biochem. Cell Biol.