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Synthesis and Biological Evaluation of 1-Arylsulfonyl-5-(N-hydroxyacrylamide)indoles as Potent Histone Deacetylase Inhibitors with Antitumor Activity in Vivo

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journal contribution
posted on 26.04.2012, 00:00 by Mei-Jung Lai, Han-Li Huang, Shiow-Lin Pan, Yi-Min Liu, Chieh-Yu Peng, Hsueh-Yun Lee, Teng-Kuang Yeh, Po-Hsien Huang, Che-Ming Teng, Ching-Shih Chen, Hsun-Yueh Chuang, Jing-Ping Liou
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 GI50 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 IC50 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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