A convenient synthesis and molecular modeling study of novel purine and pyrimidine derivatives as CDK2/cyclin A3 inhibitors
| Autor: | Abdel-Sattar S. Hamad Elgazwy, Heba S.A. El-Zahabi, Nasser S.M. Ismail |
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| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular Purine Molecular model Pyrimidine Stereochemistry Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Biochemistry Ehrlich ascites carcinoma Mice Structure-Activity Relationship chemistry.chemical_compound Cyclin-dependent kinase Catalytic Domain Cell Line Tumor Drug Discovery Animals Computer Simulation Cytotoxicity Protein Kinase Inhibitors Molecular Biology Sulfonamides Binding Sites biology Cyclin-Dependent Kinase 2 Organic Chemistry Pyrimidines chemistry Purines Docking (molecular) Enzyme inhibitor biology.protein Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry. 18:7639-7650 |
| ISSN: | 0968-0896 |
| Popis: | A series of novel purine and pyrimidine derivatives were prepared and biologically evaluated for their in vitro anti-CDK2/cyclin A3 and antitumor activities in Ehrlich ascites carcinoma (EAC) cell based assay. The novel purine derivatives 13a,b demonstrated potent inhibitor activities with IC50 values of 14 ± 9 and 13 ± 9 μM, respectively. Additionally, compound 15a showed the highest potency (IC50 = 10 ± 6 μM) in EAC cell based assay. Molecular modeling study, including fitting to a 3D-pharmacophore model and their docking into cyclin dependant kinase2 (CDK2) active site showed high fit values and docking scores. |
| Databáze: | OpenAIRE |
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