Jump to main content
Jump to site search

Issue 44, 2014
Previous Article Next Article

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

Author affiliations

Abstract

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.

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

Back to tab navigation

Supplementary files

Publication details

The article was received on 11 Mar 2014, accepted on 11 Sep 2014 and first published on 12 Sep 2014


Article type: Paper
DOI: 10.1039/C4OB00542B
Citation: Org. Biomol. Chem., 2014,12, 8966-8976
  •   Request permissions

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

    H. Lee, L. Wang, Y. Li, S. Pan, Y. Chen, C. Teng and J. Liou, Org. Biomol. Chem., 2014, 12, 8966
    DOI: 10.1039/C4OB00542B

Search articles by author

Spotlight

Advertisements