Similarities and differences in affinity and binding modes of tricyclic pyrimido- and pyrazinoxanthines at human and rat adenosine receptors
| Autor: | Jadwiga Handzlik, Christa E. Müller, Janina Karolak-Wojciechowska, Anna Drabczyńska, Katarzyna Kieć-Kononowicz, Andrzej Fruziński, Jakub Schabikowski, Agata Doroz-Płonka, Meryem Köse, Ewa Szymańska, Tadeusz Karcz |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Spectrophotometry Infrared Stereochemistry Proton Magnetic Resonance Spectroscopy Clinical Biochemistry Pharmaceutical Science CHO Cells Biochemistry 03 medical and health sciences Structure-Activity Relationship Cricetulus Drug Discovery Structure–activity relationship Animals Humans Homology modeling Amino Acid Sequence Binding site Carbon-13 Magnetic Resonance Spectroscopy Molecular Biology chemistry.chemical_classification Binding Sites Sequence Homology Amino Acid Organic Chemistry Antagonist Receptors Purinergic P1 Adenosine receptor Affinities Rats 030104 developmental biology chemistry Docking (molecular) Xanthines Molecular Medicine Tricyclic |
| Zdroj: | Bioorganicmedicinal chemistry. 24(18) |
| ISSN: | 1464-3391 |
| Popis: | A new series of 32 pyrimido- and 5 tetrahydropyrazino[2,1-f]purinediones was obtained and evaluated for their adenosine receptors (ARs) affinities. The 1,3-dibutyl derivative of 9-(4-(2-(dimethylamino)ethoxy)phenyl)-6,7,8,9-tetrahydropyrimido[1,2-f]purine-2,4(1H,3H)-dione was found to be the most potent A1 AR antagonist of the present series, showing selectivity over the other AR subtypes. The structure-activity for the obtained purinediones was established. Docking experiments of the investigated library to homology models of the human and rat A1 and A2A ARs allowed to compare the expected binding modes for selected compounds. The detailed analysis of binding cavities within individual AR subtypes indicated small but significant structural variations that may underlie the observed differences in binding affinities of purinediones at particular subtypes and species. |
| Databáze: | OpenAIRE |
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