Structure and property based design, synthesis and biological evaluation of γ-lactam based HDAC inhibitors: Part II

Chulho Lee, Eunhyun Choi, Misun Cho, Boah Lee, Soo Jin Oh, Song Kyu Park, Kiho Lee, Hwan Mook Kim, Gyoonhee Han

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17 Citations (Scopus)


Histone deacetylases (HDACs) are involved in post-translational modification and epi-genetic expression, and have been the intriguing targets for treatment of cancer. In previous study, we reported synthesis and the biological preliminary results of γ-lactam based HDAC inhibitors. Based on the previous results, smaller γ-lactam core HDAC inhibitors are more active than the corresponding series of larger δ-lactam based analogues and the hydrophobic and bulky cap groups are required for better potency which decreased microsomal stability. Thus, γ-lactam analogues with methoxy, trifluoromethyl groups of ortho-, meta-, para-positions of cap group were prepared and evaluated their biological potency. Among them, trifluoromethyl analogues, which have larger lipophilicity, showed better HDAC inhibitory activity than other analogues. In overall, lipophilicity leads to increase hydrophobic interaction between surface of HDAC active site and HDAC inhibitor, improves HDAC inhibitory activity.

Original languageEnglish
Pages (from-to)4189-4192
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number12
Publication statusPublished - 2012 Jun 15


All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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