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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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. This journal is © the Partner Organisations 2014.

Original languageEnglish
Pages (from-to)8966-8976
Number of pages11
JournalOrganic and Biomolecular Chemistry
Volume12
Issue number44
DOIs
Publication statusPublished - Nov 28 2014

Fingerprint

Histone Deacetylases
Tumors
Substitution reactions
selectivity
substitutes
HCT116 Cells
Histone Deacetylase Inhibitors
tumors
Growth
Heterografts
Antineoplastic Agents
Neoplasms
inhibitors
cells
indoline
vorinostat
3-(7-amino-1-(4-methoxyphenylsulfonyl)indolin-5-yl)-N-hydroxyacrylamide

ASJC Scopus subject areas

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

Cite this

Effect of C7-substitution of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines on the selectivity towards a subclass of histone deacetylases. / Lee, Hsueh Yun; Wang, Li Ting; Li, Yu Hsuan; Pan, Shiow Lin; Chen, Yi Lin; Teng, Che Ming; Liou, Jing Ping.

In: Organic and Biomolecular Chemistry, Vol. 12, No. 44, 28.11.2014, p. 8966-8976.

Research output: Contribution to journalArticle

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AU - Wang, Li Ting

AU - Li, Yu Hsuan

AU - Pan, Shiow Lin

AU - Chen, Yi Lin

AU - Teng, Che Ming

AU - Liou, Jing Ping

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