Synthesis, crystal structure and biological activity of beta-carboline based selective CDK4-cyclin D1 inhibitors
| Autor: | A. James Wilson, Marcos D. García, Bhabatosh Chaudhuri, Daniel P. G. Emmerson, Paul R. Jenkins, Sachin Mahale |
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| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Indoles Molecular Structure Stereochemistry beta-Carboline Organic Chemistry Cyclin-Dependent Kinase 4 Biological activity Crystal structure Crystallography X-Ray Biochemistry Fascaplysin Combinatorial chemistry chemistry.chemical_compound Inhibitory Concentration 50 Cyclin D1 chemistry Physical and Theoretical Chemistry Enzyme Inhibitors IC50 Carbolines |
| Zdroj: | Organicbiomolecular chemistry. 4(24) |
| ISSN: | 1477-0520 |
| Popis: | The design, synthesis and biological activity of a series of non-planar dihydro-beta-carboline and beta-carboline-based derivatives of the toxic anticancer agent fascaplysin is presented. We show these compounds to be selective inhibitors of CDK4 over CDK2 with an IC50 (CDK4-cyclin D1) = 11 micromol for the best compound in the series 4d. The crystallographic analysis of some of the compounds synthesised (3b/d and 4a-d) was carried out, in an effort to estimate the structural similarities between the designed inhibitors and the model compound fascaplysin. |
| Databáze: | OpenAIRE |
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