کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
443582 692738 2014 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Identification of p38α MAP kinase inhibitors by pharmacophore based virtual screening
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی تئوریک و عملی
پیش نمایش صفحه اول مقاله
Identification of p38α MAP kinase inhibitors by pharmacophore based virtual screening
چکیده انگلیسی


• Bioactive confirmations were used to develop and validate pharmacophore hypotheses.
• A combined pharmacophore model was designed to identify novel p38 MAP kinase inhibitors.
• Identified hits were biologically evaluated for p38 MAP kinase and TNF-α inhibition.
• Cytotoxicity in HepG2 cell line was determined for identified hits.

The p38α mitogen-activated protein (MAP) kinase plays a vital role in treating many inflammatory diseases. In the present study, a combined ligand and structure based pharmacophore model was developed to identify potential DFG-in selective p38 MAP kinase inhibitors. Conformations of co-crystallised inhibitors were used in the development and validation of ligand and structure based pharmacophore modeling approached. The validated pharmacophore was utilized in database screening to identify potential hits. After Lipinski's rule of five filter and molecular docking analysis, nineteen hits were purchased and selected for in vitro analysis. The virtual hits exhibited promising activity against tumor necrosis factor-α (TNF-α) with 23–98% inhibition at 10 μM concentration. Out of these seven compounds has shown potent inhibitory activity against p38 MAP kinase with IC50 values ranging from 12.97 to 223.5 nM. In addition, the toxicity study against HepG2 cells was also carried out to confirm the safety profile of identified virtual hits.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Graphics and Modelling - Volume 49, April 2014, Pages 18–24
نویسندگان
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