2. Academic Validation
  3. 2-(Phenylsulfonyl)quinoline N-hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase

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

  • Eur J Med Chem. 2016 Oct 21:122:92-101. doi: 10.1016/j.ejmech.2016.06.023.
Hsueh-Yun Lee 1,  Chih-Yi Chang 1,  Chih-Jou Su 2,  Han-Li Huang 2,  Samir Mehndiratta 1,  Yuh-Hsuan Chao 1,  Chia-Ming Hsu 2,  Sunil Kumar 1,  Ting-Yi Sung 2,  Yi-Zhen Huang 2,  Yu-Hsuan Li 1,  Chia-Ron Yang 3,  Jing-Ping Liou 4
Affiliations

Affiliations

  • 1 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
  • 2 The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
  • 3 School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: cryang@ntu.edu.tw.
  • 4 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan. Electronic address: jpl@tmu.edu.tw.
PMID: 27344487 DOI: 10.1016/j.ejmech.2016.06.023
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.

Keywords

2-(Phenylsulfonyl)quinoline; Anticancer agents; Histone deacetylase inhibitors.

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