کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1392056 1501101 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Substituted quinazolinones as kinase inhibitors endowed with anti-fibrotic properties
ترجمه فارسی عنوان
کینازولینون های جایگزین به عنوان مهار کننده های کیناز دارای خواص ضد فیبروتیک هستند
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی


• Novel 3-substituted quinazolinones have been synthesized.
• Compounds were tested against kinases involved in fibrogenic processes.
• The compounds were tested in HSCs and ISEMFs.
• Quinazolinones target multiple essential pathways of the fibrogenic process.
• The compounds reduced the expression of genes involved in fibrosis.

Some new 3-substituted quinazolinones were synthesized and evaluated as inhibitors of kinases involved in fibrogenic process. The compounds were tested against a panel of both tyrosine and serine–threonine kinases. The profile of selectivity of some representative compounds was investigated through molecular docking studies. The most interesting compounds were also evaluated in vitro as potential agents for the treatment of fibrotic diseases. Quinazolinone derivatives reduced proliferation and expression of genes involved in the fibrogenic process in hepatic stellate cells (HSCs) and intestinal subepithelial myofibroblasts (ISEMFs). Furthermore some compounds downregulated phosphorylation of p38MAPK. Our findings provide evidences that 3-substituted quinazolinones target multiple essential pathways of the fibrogenic process.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 115, 10 June 2016, Pages 416–425
نویسندگان
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