A novel series of highly potent 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitors
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
23829517
DOI
10.1021/jm4006884
Knihovny.cz E-resources
- MeSH
- Adenine analogs & derivatives chemical synthesis chemistry pharmacology MeSH
- Apoptosis MeSH
- Cyclin-Dependent Kinase 2 antagonists & inhibitors MeSH
- Cyclin-Dependent Kinases antagonists & inhibitors MeSH
- Cyclopentanes chemical synthesis chemistry pharmacology MeSH
- Phosphorylation MeSH
- Humans MeSH
- Methylamines chemical synthesis chemistry pharmacology MeSH
- Models, Molecular MeSH
- Cell Line, Tumor MeSH
- Computer Simulation MeSH
- CDC2 Protein Kinase antagonists & inhibitors MeSH
- Antineoplastic Agents chemical synthesis chemistry pharmacology MeSH
- Purines chemical synthesis chemistry pharmacology MeSH
- Retinoblastoma Protein metabolism MeSH
- Drug Screening Assays, Antitumor 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
- Adenine MeSH
- Cyclin-Dependent Kinase 2 MeSH
- Cyclin-Dependent Kinases MeSH
- Cyclopentanes MeSH
- Methylamines MeSH
- N2-(4-aminocyclohexyl)-9-cyclopentyl-N6-(6-(2-hydroxyphenyl)pyridin-3-ylmethyl)-9H-purine-2,6-diamine MeSH Browser
- CDC2 Protein Kinase MeSH
- Antineoplastic Agents MeSH
- Purines MeSH
- Retinoblastoma Protein MeSH
The inhibition of overactive CDKs during cancer remains an important strategy in cancer drug development. We synthesized and screened a novel series of 2-substituted-6-biarylmethylamino-9-cyclopentylpurine derivatives for improved CDK inhibitory activity and antiproliferative effects. One of the most potent compounds, 6b, exhibited strong cytotoxicity in the human melanoma cell line G361 that correlated with robust CDK1 and CDK2 inhibition and caspase activation. In silico modeling of 6b in the active site of CDK2 revealed a high interaction energy, which we believe is due to the 6-heterobiarylmethylamino substitution of the purine moiety.
References provided by Crossref.org
Adamantane-Substituted Purines and Their β-Cyclodextrin Complexes: Synthesis and Biological Activity
