Design, synthesis and biological evaluation of quinoline derivatives as HDAC class I inhibitors

Chen Chen, Xuben Hou, Guohua Wang, Wenyan Pan, Xinying Yang, Yingkai Zhang, Hao Fang

Research output: Contribution to journalArticlepeer-review


Inhibition of histone deacetylase (HDAC) has been regarded as a potential therapeutic approach for treatment of multiple diseases including cancer. Based on pharmacophore model of HDAC inhibitors, a series of quinoline-based N-hydroxycinnamamides and N-hydroxybenzamides were designed and synthesized as potent HDAC inhibitors. All target compounds were evaluated for their in vitro HDAC inhibitory activities and anti-proliferative activities and the best compound 4a surpass Vorinostat in both enzymatic inhibitory activity and cellular anti-proliferative activity. In terms of HDAC isoforms selectivity, compounds 4a exhibited preferable inhibition for class I HDACs, especially for HDAC8, the IC50 value (442 nM) was much lower than that of Vorinostat (7468 nM). Subsequently, we performed class I & IIa HDACs whole cell enzyme assay to evaluate inhibitory activity in whole cell context. Compounds 4a and 4e displayed much better cellular activity for class I HDACs than that for class IIa HDACs, which indicated that 4a and 4e might be potent class I HDAC inhibitors. Meanwhile, flow cytometry analysis showed that compound 4a and 4e can promote cell apoptosis in vitro.

Original languageEnglish (US)
Pages (from-to)11-23
Number of pages13
JournalEuropean journal of medicinal chemistry
StatePublished - 2017


  • Anti-proliferative
  • Class I HDACs
  • Class I celluar activity
  • Hydroxamic acid
  • Pro-apoptosis activity
  • Quinoline

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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