Synthesis and biological evaluation of 2-quinolineacrylamides

Bioorg Med Chem. 2020 Feb 1;28(3):115250. doi: 10.1016/j.bmc.2019.115250. Epub 2019 Dec 19.

Abstract

A series of C6-substituted N-hydroxy-2-quinolineacrylamides (3-15), with four types of bridging groups have been synthesized. Most of these compounds exhibit antiproliferative activity against A549 and HCT116 cells and Western blot analysis revealed that they are able to inhibit HDAC. Measurement of the HDAC isoform activity of ether-containing compounds showed that compound 9 has distinct HDAC6 selectivity, more than 300-fold over other isoforms. This paper describes the development of 6-aryloxy-N-hydroxy-2-quinolineacrylamides as potential HDAC6 inhibitors.

Keywords: 2-Quinolineacrylamide; Histone deacetylase; Ullmann reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Acrylamides / chemical synthesis
  • Acrylamides / chemistry
  • Acrylamides / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HCT116 Cells
  • Histone Deacetylase 6 / antagonists & inhibitors*
  • Histone Deacetylase 6 / metabolism
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Quinolines / chemical synthesis
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Acrylamides
  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Quinolines
  • quinoline
  • HDAC6 protein, human
  • Histone Deacetylase 6