Open AccessSynthesis and Biological Evaluation of 1-Arylsulfonyl-5-(N-hydroxyacrylamide)indoles as Potent Histone Deacetylase Inhibitors with Antitumor Activity in Vivo
Author(s) -
Mei-Jung Lai,
Han-Li Huang,
ShiowLin Pan,
Yi-Min Liu,
Chieh-Yu Peng,
HsuehYun Lee,
Teng-Kuang Yeh,
Po-Hsien Huang,
CheMing Teng,
Ching-Shih Chen,
HsunYueh Chuang,
JingPing Liou
Publication year - 2012
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/jm300197a
Subject(s) - chemistry , histone deacetylase , in vivo , pharmacology , in vitro , a549 cell , hdac1 , cell culture , stereochemistry , histone , biochemistry , biology , genetics , microbiology and biotechnology , gene
A series of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indoles has been identified as a new class of histone deacetylase inhibitors. Compounds 8, 11, 12, 13, and 14 demonstrated stronger antiproliferative activities than 1 (SAHA) with GI(50) values ranging from 0.36 to 1.21 μM against Hep3B, MDA-MB-231, PC-3, and A549 human cancer cell lines. Lead compound 8 showed remarkable HDAC 1, 2, and 6 isoenzymes inhibitory activities with IC(50) values of 12.3, 4.0, 1.0 nM, respectively, which are comparable to 1. In in vivo efficacy evaluation against lung A549 xenograft model, 8 displayed better antitumor activity than compound 1.
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