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1,2,4-Trisubstituted imidazolinones with dual carbonic anhydrase and p38 mitogen-activated protein kinase inhibitory activity
- Source :
- Bioorganic chemistry. 82
- Publication Year :
- 2018
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 10902120
- Volume :
- 82
- Database :
- OpenAIRE
- Journal :
- Bioorganic chemistry
- Accession number :
- edsair.doi.dedup.....c807476ee5cd6f5d827f35a1a14ad97f