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

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Title
Structure and property based design, synthesis and biological evaluation of γ-lactam based HDAC inhibitors: Part II
Author(s)
C Lee; E Choi; M Cho; B Lee; Soo Jin Oh; S K Park; K Lee; H M Kim; G Han
Bibliographic Citation
Bioorganic & Medicinal Chemistry Letters, vol. 22, no. 12, pp. 4189-4192
Publication Year
2012
Abstract
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.
Keyword
DockingHistone deacetylasesInhibitorOptimizationProperty
ISSN
0960-894X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bmcl.2012.04.045
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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