1,2,4-Trisubstituted imidazolinones with dual carbonic anhydrase and p38 mitogen-activated protein kinase inhibitory activity
| Autor: | Emanuela Berrino, Hanan H. Georgey, Fatma M. Manhi, Nehad A. Mohamed, Walaa R. Mahmoud, Claudiu T. Supuran |
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| Rok vydání: | 2018 |
| Předmět: |
Gene isoform
Sorafenib p38 mitogen-activated protein kinases Inhibitory postsynaptic potential 01 natural sciences Biochemistry p38 Mitogen-Activated Protein Kinases Structure-Activity Relationship Carbonic anhydrase Drug Discovery medicine Humans Protein kinase A Carbonic Anhydrase Inhibitors Imidazolines Molecular Biology Protein Kinase Inhibitors Carbonic Anhydrases Enzyme Assays chemistry.chemical_classification Sulfonamides biology Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry 0104 chemical sciences Isoenzymes 010404 medicinal & biomolecular chemistry Enzyme biology.protein Acetazolamide medicine.drug |
| Zdroj: | Bioorganic chemistry. 82 |
| ISSN: | 1090-2120 |
| Popis: | Various 1,2,4 trisubstituted imidazolin-5-one derivatives were synthesized and evaluated for their inhibitory activity against p38 mitogen-activated protein kinase (p38MAPK) and carbonic anhydrase (CA) enzymes aiming to explore potential dual inhibitors. Results revealed that compounds 3c, 3g, 3h, 4a, 6c and 6d were the most effective derivatives against p38αMAPK (IC50 = 0.14, 0.14, 0.056, 0.14, 0.13 and 0.14 μM, respectively) compared to sorafenib (IC50 = 1.58 μM) as standard drug. On the other hand, compound 4a revealed the best inhibitory activity against all the tested carbonic anhydrase isoforms CA I, II, IV and IX with Ki values of 95.0, 0.83, 6.90 and 12.4 nM, respectively compared to acetazolamide with Ki values 250, 12.1, 74 and 12.8 nM, respectively. Therefore, compound 4a can be considered as a potent dual p38αMAPK/CA inhibitor. |
| Databáze: | OpenAIRE |
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