Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors

Wei Jan Huang, Ching Chow Chen, Shi Wei Chao, Chia Chun Yu, Chen Yui Yang, Jih Hwa Guh, Yun Chieh Lin, Chiao I. Kuo, Ping Yang, Chung I. Chang

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25 Citations (Scopus)


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 languageEnglish
Pages (from-to)4042-4049
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Issue number9
Publication statusPublished - Sep 2011



  • Histone deacetylase
  • LBH-589
  • Molecular modeling
  • Osthole
  • SAHA

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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