Synthesis and discovery of new compounds bearing coumarin scaffold for the treatment of pulmonary fibrosis.
Eur J Med Chem
; 185: 111790, 2020 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-31699535
ABSTRACT
Idiopathic pulmonary fibrosis, characterized by excess accumulation of extracellular matrix, involved in many chronic diseases or injuries, threatens human health greatly. We have reported a series of compounds bearing coumarin scaffold which potently inhibited TGF-ß-induced total collagen accumulation in NRK-49F cell line and migration of macrophages. Compound 9d also suppressed the TGF-ß-induced protein expression of COL1A1, α-SMA, and p-Smad3 in vitro. Meanwhile, 9d at a dose of 100â¯mg/kg/day through oral administrations for 4 weeks effectively alleviated infiltration of inflammatory cells in lung tissue and fibrotic degree in bleomycin-induced pulmonary fibrosis model, which may related to its inhibition of TGF-ß/Smad3 pathway and anti-inflammation efficacy. In addition, 9d demonstrated decent bioavailability (Fâ¯=â¯39.88%) and suitable eliminated half-life time (T1/2â¯=â¯13.09â¯h), suggesting that 9d could be a potential drug candidate for the treatment of fibrotic diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrose Pulmonar
/
Cumarínicos
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Descoberta de Drogas
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article