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Eur J Med Chem. 2016 Oct 21;122:92-101. doi: 10.1016/j.ejmech.2016.06.023. Epub 2016 Jun 16.

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

Author information

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.

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

PMID:
27344487
DOI:
10.1016/j.ejmech.2016.06.023
[Indexed for MEDLINE]

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