Novel arylazopyrazole inhibitors of cyclin-dependent kinases
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25835357
DOI
10.1016/j.bmc.2015.03.025
PII: S0968-0896(15)00209-6
Knihovny.cz E-resources
- Keywords
- Cell cycle, Cyclin-dependent kinases, Inhibitor, Selectivity,
- MeSH
- Apoptosis drug effects MeSH
- K562 Cells MeSH
- Cyclin-Dependent Kinases antagonists & inhibitors metabolism MeSH
- Protein Kinase Inhibitors chemical synthesis chemistry pharmacology MeSH
- Humans MeSH
- MCF-7 Cells MeSH
- Molecular Structure MeSH
- Cell Proliferation drug effects MeSH
- Pyrazoles chemical synthesis chemistry pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cyclin-Dependent Kinases MeSH
- Protein Kinase Inhibitors MeSH
- Pyrazoles MeSH
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.
References provided by Crossref.org
Modification of Boc-Protected CAN508 via Acylation and Suzuki-Miyaura Coupling
