Bioorganic & medicinal chemistry, 2015-05, Vol.23 (9), p.1975-1981
2015
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- Autor(en) / Beteiligte
- Titel
- Novel arylazopyrazole inhibitors of cyclin-dependent kinases
- Ist Teil von
- Bioorganic & medicinal chemistry, 2015-05, Vol.23 (9), p.1975-1981
- Ort / Verlag
- England: Elsevier Ltd
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- [Display omitted] Here, we describe new 4-arylazo-3,5-diamino-1H-pyrazole derivatives developed from CAN508, one of the first inhibitors to show preference for transcriptional regulator cyclin-dependent kinase 9. By substituting nitrogen in the pyrazole ring and employing a heteroatom in the 4-aryl ring, we obtained more potent derivatives differing in their CDK-selectivity profiles. The antiproliferative and anti-CDK kinase activities of the novel arylazopyrazoles were examined. The cellular effect of compound IVc was studied on MCF-7 cells synchronized by various methods and compared with other selective CDK inhibitors. The results demonstrated that IVc shows a preference for CDK4 and CDK1. In contrast to cytostatic effects induced by IVc in MCF-7 and K562 cells, we observed apoptotic activities in the RPMI-8226 cell line, which were confirmed by detecting active caspases by different biochemical assays.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0968-0896eISSN: 1464-3391DOI: 10.1016/j.bmc.2015.03.025Titel-ID: cdi_pubmed_primary_25835357
- Format
- –
- Schlagworte
- Apoptosis - drug effects, Cell cycle, Cell Proliferation - drug effects, Cyclin-dependent kinases, Cyclin-Dependent Kinases - antagonists & inhibitors, Cyclin-Dependent Kinases - metabolism, Dose-Response Relationship, Drug, Humans, Inhibitor, K562 Cells, MCF-7 Cells, Molecular Structure, Protein Kinase Inhibitors - chemical synthesis, Protein Kinase Inhibitors - chemistry, Protein Kinase Inhibitors - pharmacology, Pyrazoles - chemical synthesis, Pyrazoles - chemistry, Pyrazoles - pharmacology, Selectivity, Structure-Activity Relationship