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

نویسندگان

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

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.

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عنوان ژورنال:
  • Organic & biomolecular chemistry

دوره 12 44  شماره 

صفحات  -

تاریخ انتشار 2014