Synthesis and biological evaluation of 1-arylsulfonyl-5-(N -hydroxyacrylamide)indoles as potent histone deacetylase inhibitors with antitumor activity in vivo

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

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3777-3791
Number of pages15
JournalJournal of Medicinal Chemistry
Volume55
Issue number8
DOIs
Publication statusPublished - Apr 26 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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