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

doi:10.1016/j.ejmech.2016.06.023

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

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27 Citations (Scopus)

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 GI₅₀values 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.

Original language	English
Pages (from-to)	92-101
Number of pages	10
Journal	European Journal of Medicinal Chemistry
Volume	122
DOIs	https://doi.org/10.1016/j.ejmech.2016.06.023
Publication status	Published - 2016

Keywords

2-(Phenylsulfonyl)quinoline
Anticancer agents
Histone deacetylase inhibitors

ASJC Scopus subject areas

Drug Discovery
Pharmacology
Organic Chemistry

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10.1016/j.ejmech.2016.06.023

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Lee, H. Y., Chang, C. Y., Su, C. J., Huang, H. L., Mehndiratta, S., Chao, Y. H., Hsu, C. M., Kumar, S., Sung, T. Y., Huang, Y. Z., Li, Y. H., Yang, C. R., & Liou, J. P. (2016). 2-(Phenylsulfonyl)quinoline N-hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase. European Journal of Medicinal Chemistry, 122, 92-101. https://doi.org/10.1016/j.ejmech.2016.06.023

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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 GI50values 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.",

keywords = "2-(Phenylsulfonyl)quinoline, Anticancer agents, Histone deacetylase inhibitors",

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

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year = "2016",

doi = "10.1016/j.ejmech.2016.06.023",

language = "English",

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pages = "92--101",

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AU - Lee, Hsueh Yun

AU - Chang, Chih Yi

AU - Su, Chih Jou

AU - Huang, Han Li

AU - Mehndiratta, Samir

AU - Chao, Yuh Hsuan

AU - Hsu, Chia Ming

AU - Kumar, Sunil

AU - Sung, Ting Yi

AU - Huang, Yi Zhen

AU - Li, Yu Hsuan

AU - Yang, Chia Ron

AU - Liou, Jing Ping

PY - 2016

Y1 - 2016

N2 - 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 GI50values 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.

AB - 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 GI50values 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.

KW - 2-(Phenylsulfonyl)quinoline

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KW - Histone deacetylase inhibitors

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ER -

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

Abstract

Keywords

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