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
  • 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: [email protected].
  • 4. School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan. Electronic address: [email protected].
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.