2-(Phenylsulfonyl)quinoline N-hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase

Hsueh Yun Lee, Chih Yi Chang, Chih Jou Su, Han Li Huang, Samir Mehndiratta, Yuh Hsuan Chao, Chia Ming Hsu, Sunil Kumar, Ting Yi Sung, Yi Zhen Huang, Yu Hsuan Li, Chia Ron Yang, Jing Ping Liou

研究成果: 雜誌貢獻文章

4 引文 (Scopus)

摘要

This study reports the design and synthesis of 2-(phenylsulfonyl)quinoline N-hydroxyacrylamides (8a–k). Structure-activity relationship studies focusing on regio-effect of N-hydroxyacrylamide moiety and influence of the sulfonyl linker revealed that N-hydroxy-3-[3-(quinoline-2-sulfonyl)-phenyl]-acrylamide (8f) showed remarkable enzymatic and cellular activity. The GI50 values of 8f for HL-60, HCT116, PC-3, and A549 cells were found to be 0.29, 0.08, 0.15, and 0.27 μM, respectively. The compounds are therefore more potent than FDA approved PXD-101 and SAHA. They also have an effect on the acetylation degree of histone H3 and α-tubulin. In in vivo studies, 8f showed marked inhibition of the growth of HCT116 xenografts.

原文英語
頁(從 - 到)92-101
頁數10
期刊European Journal of Medicinal Chemistry
122
DOIs
出版狀態已發佈 - 十月 21 2016

指紋

Histone Deacetylases
Antineoplastic Agents
Acetylation
Acrylamide
Structure-Activity Relationship
Tubulin
Heterografts
Histones
Growth
quinoline
A549 Cells

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

引用此文

2-(Phenylsulfonyl)quinoline N-hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase. / Lee, Hsueh Yun; Chang, Chih Yi; Su, Chih Jou; Huang, Han Li; Mehndiratta, Samir; Chao, Yuh Hsuan; Hsu, Chia Ming; Kumar, Sunil; Sung, Ting Yi; Huang, Yi Zhen; Li, Yu Hsuan; Yang, Chia Ron; Liou, Jing Ping.

於: European Journal of Medicinal Chemistry, 卷 122, 21.10.2016, p. 92-101.

研究成果: 雜誌貢獻文章

Lee, Hsueh Yun ; Chang, Chih Yi ; Su, Chih Jou ; Huang, Han Li ; Mehndiratta, Samir ; Chao, Yuh Hsuan ; Hsu, Chia Ming ; Kumar, Sunil ; Sung, Ting Yi ; Huang, Yi Zhen ; Li, Yu Hsuan ; Yang, Chia Ron ; Liou, Jing Ping. / 2-(Phenylsulfonyl)quinoline N-hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase. 於: European Journal of Medicinal Chemistry. 2016 ; 卷 122. 頁 92-101.
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abstract = "This study reports the design and synthesis of 2-(phenylsulfonyl)quinoline N-hydroxyacrylamides (8a–k). Structure-activity relationship studies focusing on regio-effect of N-hydroxyacrylamide moiety and influence of the sulfonyl linker revealed that N-hydroxy-3-[3-(quinoline-2-sulfonyl)-phenyl]-acrylamide (8f) showed remarkable enzymatic and cellular activity. The GI50 values of 8f for HL-60, HCT116, PC-3, and A549 cells were found to be 0.29, 0.08, 0.15, and 0.27 μM, respectively. The compounds are therefore more potent than FDA approved PXD-101 and SAHA. They also have an effect on the acetylation degree of histone H3 and α-tubulin. In in vivo studies, 8f showed marked inhibition of the growth of HCT116 xenografts.",
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AU - Mehndiratta, Samir

AU - Chao, Yuh Hsuan

AU - Hsu, Chia Ming

AU - Kumar, Sunil

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AU - Huang, Yi Zhen

AU - Li, Yu Hsuan

AU - Yang, Chia Ron

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