Synthesis, CYP 450 evaluation, and docking simulation of novel 4-aminopyridine and coumarin derivatives
| Autor: | Hamid R. Sohbati, Saeed Balalaie, Homa Azizian, Mohammad S. Alavijeh, Hajar G. Ghalehshahi |
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| Rok vydání: | 2018 |
| Předmět: |
Potassium Channels
Stereochemistry Pharmaceutical Science 01 natural sciences Isozyme Hydrophobic effect chemistry.chemical_compound Cytochrome P-450 Enzyme System In vivo Central Nervous System Diseases Coumarins Amide Pyridine Drug Discovery Humans 4-Aminopyridine Molecular Structure 010405 organic chemistry Coumarin Pyrone 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry chemistry Docking (molecular) Protein Binding |
| Zdroj: | Archiv der Pharmazie. 352(3) |
| ISSN: | 1521-4184 |
| Popis: | Four series of novel compounds based on 4-aminopyridine, glatiramer acetate, pyrone, and coumarin backbones were sufficiently synthesized and identified by spectroscopic methods. CYP enzyme inhibition assays of five predominate human P450 isozymes indicate that all compounds, except for 4-hydrazide pyridine 1c, seem to be less toxic than 4-aminopyridine. Further investigation of the compounds using molecular docking experiments revealed different, the same, or stronger binding modes for most of the synthesized compounds, with both polar and hydrophobic interactions with the 1WDA and 1J95 receptors compared to benzoyl l-arginine amide and 4-aminopyridine, respectively. These results introduce the synthesized compounds as K+ channel blockers that could be considered for in vivo CNS disease studies. |
| Databáze: | OpenAIRE |
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