Synthesis and biological evaluation of analogues of butyrolactone I and molecular model of its interaction with CDK2
| Autor: | Miguel F. Braña, M. Luisa García, Ana Ramos, Jose M. Pozuelo, M. Teresa Domínguez, Beatriz de Pascual-Teresa, Berta López |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Models
Molecular Molecular model Stereochemistry Biochemistry Molecular dynamics chemistry.chemical_compound 4-Butyrolactone Cell Line Tumor Humans Aspergillus terreus Physical and Theoretical Chemistry Protein Kinase Inhibitors Cell Proliferation Binding Sites Natural product biology Organic Chemistry Cyclin-dependent kinase 2 Butyrolactone I Active site Esters biology.organism_classification Protein Structure Tertiary chemistry Docking (molecular) biology.protein |
| Zdroj: | Org. Biomol. Chem.. 2:1864-1871 |
| ISSN: | 1477-0539 1477-0520 |
| Popis: | A series of analogues of butyrolactone I, a natural product isolated from Aspergillus terreus that selectively inhibits the CDK2 and CDK1 kinases and that has been found to exhibit an interesting antiproliferative activity, have been synthesized. Its antitumor activity has been tested. Molecular models of the complex between butyrolactone I and the CDK2 active site have been built using a combination of conformational search and automated docking techniques. The stability of the resulting complexes has been assessed by molecular dynamics simulations and the experimental results obtained for the synthesized analogues are rationalized based on the molecular models. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|