6-Imino-2-thioxo-pyrimidinones as a new class of dipeptidyl peptidase IV inhibitors
| Autor: | Krunoslav Nujić, Krunoslav Kovačević, Višnja Stepanić, Dubravko Jelić, Donatella Verbanac |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
chemistry.chemical_classification
Stereochemistry Organic Chemistry Dipeptidyl peptidase Homologous series chemistry.chemical_compound Pyrimidinones Enzyme chemistry DPP IV inhibitor pyrimidinone enzyme kinetics molecular docking cytotoxicity Enzyme kinetics General Pharmacology Toxicology and Pharmaceutics Glycoprotein Cytotoxicity Alkyl |
| Popis: | Dipeptidyl peptidase IV is a glycoprotein which removes N-terminal dipeptides from physiologically relevant polypeptides. An homologous series of 6-imino-2-thioxo-5-{; ; [3, 4, 5-tris(methyloxy)phenyl]methyl}; ; -2, 5-dihydro-4(3H)-pyrimidinones has been tested for inhibition of DPP IV activity. The inhibitory effects at 0.1 mM were observed. Enzyme kinetic studies revealed that compounds inhibit DPP IV activity competitively. According to the molecular docking analysis, the inhibitors are anchored into the DPP IV hydrolytic site by interactions of the pyrimidinone core with Glu206, Tyr662, and Tyr547, with the alkyl chain entering the S1 pocket. We conclude that pyrimidinone-like compounds are a promising new scaffold for reversible inhibition of DPP IV. |
| Databáze: | OpenAIRE |
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