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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• 作者：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
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：April 26, 2012
• 年：2012
• 卷：55
• 期：8
• 页码：3777-3791
• 全文大小：511K
• 年卷期：v.55,no.8(April 26, 2012)
• ISSN：1520-4804

文摘

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 渭M 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.