Effect of C7-substitution of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines on the selectivity towards a subclass of histone deacetylases

Hsueh Yun Lee, Li Ting Wang, Yu Hsuan Li, Shiow Lin Pan, Yi Lin Chen, Che Ming Teng, Jing Ping Liou

研究成果: 雜誌貢獻文章

6 引文 斯高帕斯(Scopus)

摘要

This study focused on the substitution effect at position C7 of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines. Compound 9, (E)-3-(7-amino-1-(4-methoxyphenylsulfonyl)indolin-5-yl)-N-hydroxyacrylamide, displayed 4- to 14-fold more potent antiproliferative activity than vorinostat (SAHA, 1). Notably, 9 possessed specific histone deacetylase (HDAC) inhibitory activity toward HDAC1 and HDAC2, but had no effect on HDAC6, indicating that 9 has the potential to be developed as a class I HDAC inhibitor. In a xenograft tumor model, 9 suppressed the growth of HCT116 cells at 100 mg kg-1, which led to a TGI (tumor growth inhibition) of 40.3%. Taken together, the C7 substitutions have a crucial effect on class I HDACs, which is beneficial for synthesizing efficient anticancer agents. This journal is © the Partner Organisations 2014.
原文英語
頁(從 - 到)8966-8976
頁數11
期刊Organic and Biomolecular Chemistry
12
發行號44
DOIs
出版狀態已發佈 - 十一月 28 2014

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry
  • Medicine(all)

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