Identification of p38α MAP kinase inhibitors by pharmacophore based virtual screening
Research output: Contribution to journal › Journal article › Research › peer-review
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 10μM concentration. Out of these seven compounds has shown potent inhibitory activity against p38 MAP kinase with IC50 values ranging from 12.97 to 223.5nM. In addition, the toxicity study against HepG2 cells was also carried out to confirm the safety profile of identified virtual hits.
Original language | English |
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Journal | Journal of Molecular Graphics and Modelling |
Volume | 49 |
Pages (from-to) | 18-24 |
Number of pages | 7 |
ISSN | 1093-3263 |
DOIs | |
Publication status | Published - Apr 2014 |
- Hep G2 Cells, Humans, Protein Kinase Inhibitors, Structure-Activity Relationship, Tumor Necrosis Factor-alpha, p38 Mitogen-Activated Protein Kinases, Journal Article, Research Support, Non-U.S. Gov't
Research areas
ID: 168217475