4-Hydroxy-3-methylbenzofuran-2-carbohydrazones as novel LSD1 inhibitors

Bioorg Med Chem Lett. 2020 May 15;30(10):127109. doi: 10.1016/j.bmcl.2020.127109. Epub 2020 Mar 13.

Abstract

Histone lysine specific demethylase 1 (LSD1 or KDM1A) is a potential therapeutic target in oncology due to its overexpression in various human tumors. We report herein a new class of benzofuran acylhydrazones as potent LSD1 inhibitors. Among the 31 compounds prepared, 14 compounds exhibited excellent LSD1 inhibitory activity with IC50 values ranging from 7.2 to 68.8 nM. In cellular assays, several compounds inhibited the proliferations of various cancer cell lines, including PC-3, MCG-803, U87 MG, PANC-1, HT-29 and MCF-7. This opens up the opportunity for further optimization and investigation of this class compounds for potential cancer treatment.

Keywords: Anti-tumor activity; Benzofuran; Epigenetics; Lysine-specific demethylase 1; N-acylhydrazone (NAH).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzofurans / chemistry*
  • Binding Sites
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Histone Demethylases / antagonists & inhibitors*
  • Histone Demethylases / metabolism
  • Humans
  • Hydrazones / chemistry*
  • Hydrazones / metabolism
  • Hydrazones / pharmacology
  • Inhibitory Concentration 50
  • Molecular Docking Simulation
  • Structure-Activity Relationship

Substances

  • Benzofurans
  • Enzyme Inhibitors
  • Hydrazones
  • Histone Demethylases
  • KDM1A protein, human
  • benzofuran