Synthesis and biological activity of optically active NCL-1, a lysine-specific demethylase 1 selective inhibitor

Bioorg Med Chem. 2011 Jun 15;19(12):3702-8. doi: 10.1016/j.bmc.2010.12.024. Epub 2010 Dec 22.

Abstract

Optically active (1S,2R)-NCL-1 and (1R,2S)-NCL-1 were synthesized and evaluated for their lysine-specific demethylase 1 inhibitory activity and cell growth inhibitory activity. In enzyme assays, the (1S,2R)-isomer was approximately four times more potent than the (1R,2S)-isomer. In cell growth inhibition assays, the two isomers showed similar activity in HEK293 cells and SH-SY5Y cells, whereas the (1S,2R)-isomer showed approximately four times more potent activity than the (1R,2S)-isomer in HeLa cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides / chemical synthesis*
  • Benzamides / chemistry
  • Benzamides / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Cyclopropanes / chemical synthesis*
  • Cyclopropanes / chemistry
  • Cyclopropanes / pharmacology*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Growth Inhibitors / chemical synthesis
  • Growth Inhibitors / chemistry
  • Growth Inhibitors / pharmacology
  • HEK293 Cells
  • HeLa Cells
  • Histone Demethylases / antagonists & inhibitors*
  • Humans
  • Inhibitory Concentration 50
  • Lysine / chemistry*
  • Magnetic Resonance Spectroscopy
  • Stereoisomerism
  • Substrate Specificity

Substances

  • 2-(3-(3-benzamido-4-(benzylamino)-4-oxobutoxy)phenyl)cyclopropylamine
  • Benzamides
  • Cyclopropanes
  • Enzyme Inhibitors
  • Growth Inhibitors
  • Histone Demethylases
  • Lysine