"Dual Anta-Inhibitors" of the A2A Adenosine Receptor and Casein Kinase CK1delta : Synthesis, Biological Evaluation, and Molecular Modeling Studies
Based on a screening of a chemical library of A2A adenosine receptor (AR) antagonists, a series of di- and tri-substituted adenine derivatives were synthesized and tested for their ability to inhibit the activity of the enzyme casein kinase 1 delta (CK1δ) and to bind adenosine receptors (ARs). Some derivatives, here called "dual anta-inhibitors", demonstrated good CK1δ inhibitory activity combined with a high binding affinity, especially for the A2AAR. The N6-methyl-(2-benzimidazolyl)-2-dimethyamino-9-cyclopentyladenine (17, IC50 = 0.59 μM and KiA2A = 0.076 μM) showed the best balance of A2AAR affinity and CK1δ inhibitory activity. Computational studies were performed to simulate, at the molecular level, the protein-ligand interactions involving the compounds of our series. Hence, the dual anta-inhibitor 17 could be considered the lead compound of new therapeutic agents endowed with synergistic effects for the treatment of chronic neurodegenerative and cancer diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Pharmaceuticals (Basel, Switzerland) - 16(2023), 2 vom: 23. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Spinaci, Andrea [VerfasserIn] |
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| Links: |
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| Themen: |
“dual anta-inhibitors” |
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| Anmerkungen: |
Date Revised 03.06.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/ph16020167 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357614275 |
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| 520 | |a Based on a screening of a chemical library of A2A adenosine receptor (AR) antagonists, a series of di- and tri-substituted adenine derivatives were synthesized and tested for their ability to inhibit the activity of the enzyme casein kinase 1 delta (CK1δ) and to bind adenosine receptors (ARs). Some derivatives, here called "dual anta-inhibitors", demonstrated good CK1δ inhibitory activity combined with a high binding affinity, especially for the A2AAR. The N6-methyl-(2-benzimidazolyl)-2-dimethyamino-9-cyclopentyladenine (17, IC50 = 0.59 μM and KiA2A = 0.076 μM) showed the best balance of A2AAR affinity and CK1δ inhibitory activity. Computational studies were performed to simulate, at the molecular level, the protein-ligand interactions involving the compounds of our series. Hence, the dual anta-inhibitor 17 could be considered the lead compound of new therapeutic agents endowed with synergistic effects for the treatment of chronic neurodegenerative and cancer diseases | ||
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| 700 | 1 | |a Cui, Chang |e verfasserin |4 aut | |
| 700 | 1 | |a Colotta, Vittoria |e verfasserin |4 aut | |
| 700 | 1 | |a Dal Ben, Diego |e verfasserin |4 aut | |
| 700 | 1 | |a Cescon, Eleonora |e verfasserin |4 aut | |
| 700 | 1 | |a Francucci, Beatrice |e verfasserin |4 aut | |
| 700 | 1 | |a Grieco, Ilenia |e verfasserin |4 aut | |
| 700 | 1 | |a Lambertucci, Catia |e verfasserin |4 aut | |
| 700 | 1 | |a Marucci, Gabriella |e verfasserin |4 aut | |
| 700 | 1 | |a Bassani, Davide |e verfasserin |4 aut | |
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