Abstract
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.
Original language | English |
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Pages (from-to) | 4042-4049 |
Number of pages | 8 |
Journal | European Journal of Medicinal Chemistry |
Volume | 46 |
Issue number | 9 |
DOIs | |
Publication status | Published - Sept 2011 |
Keywords
- Histone deacetylase
- LBH-589
- Molecular modeling
- Osthole
- SAHA
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry
- Pharmacology