Pyrrolo[2,3-a]carbazoles as Potential Cyclin Dependent Kinase 1 (CDK1) Inhibitors. Synthesis, Biological Evaluation, and Binding Mode through Docking Simulations
| Autor: | Maria Manioudaki, Manolis A. Fousteris, Evgenia Lampropoulou, Georgios A. Spyroulias, Evangelia Papadimitriou, Athanasios Papakyriakou, Sotiris S. Nikolaropoulos, Anna I. Koutsourea |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Cyclin-dependent kinase 1 Binding Sites Molecular model biology Stereochemistry Chemistry Carbazoles Chemical synthesis Structure-Activity Relationship Docking (molecular) Cyclin-dependent kinase CDC2 Protein Kinase Drug Discovery biology.protein Molecular Medicine Structure–activity relationship Pyrroles Binding site Protein Binding |
| Zdroj: | Journal of Medicinal Chemistry. 51:1048-1052 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm0700666 |
| Popis: | Pyrrolo[2,3- a]carbazole derivatives were synthesized, and their effects on CDK1/cyclinB activity were evaluated. The most potent and efficacious inhibitor was found to be ethyl 9-chloro-1H-pyrrolo[2,3-alpha]carbazole-2-carboxylate (1e), exhibiting an IC50 in the low micromolar range and leading to 90% at higher concentrations. Using a computational model for CDK1-1e, binding we have observed that 1e exhibited two likely binding modes in the ATP-binding cleft that involve interactions with Lys130, Thr14, and Asp146 of the enzyme. |
| Databáze: | OpenAIRE |
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