Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors
| Autor: | Yun Chieh Lin, Chen Yui Yang, Chiao I. Kuo, Ching-Chow Chen, Chia Chun Yu, Shi Wei Chao, Jih-Hwa Guh, Ping Yang, Chung-I Chang, Wei Jan Huang |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Pharmacology
Gene isoform Spectrometry Mass Electrospray Ionization Vorinostat Molecular model Stereochemistry Chemistry Protein Conformation Organic Chemistry Blotting Western HDAC8 General Medicine Hydroxamic Acids HDAC1 Histone Deacetylases Histone Deacetylase Inhibitors Cell culture Drug Discovery Potency Humans Histone deacetylase Human cancer |
| Zdroj: | European journal of medicinal chemistry. 46(9) |
| ISSN: | 1768-3254 |
| Popis: | Our previous studies have demonstrated that osthole, a Chinese herbal compound, could be incorporated into the hydroxycinnamide scaffold of LBH-589, a potent HDAC inhibitor, as an effective hydrophobic cap; the resulting compounds showed significant potency against several HDAC isoforms. Here, we presented a series of osthole derivatives fused with the aliphatic-hydroxamate core of suberoylanilide hydroxamic acid (SAHA), a clinically-approved HDAC inhibitor. Several compounds showed potent activity against nuclear HDACs. Further assays against individual HDAC isoforms revealed that some compounds showed not only SAHA-like activity towards HDAC1, -4 and -6, they inhibited HDAC8 by log difference than SAHA and thus exhibited a broader HDAC inhibition spectrum. Among them, compound 6g showed potent antiproliferative effect on several human cancer cell lines. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect