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.
Daisuke Ogasawara  1 ,  Takayoshi Suzuki ,  Koshiki Mino ,  Rie Ueda ,  Mohammed Naseer Ahmed Khan ,  Takuya Matsubara ,  Koichi Koseki ,  Makoto Hasegawa ,  Ryuzo Sasaki ,  Hidehiko Nakagawa ,  Tamio Mizukami ,  Naoki Miyata
Affiliations
  • 1. Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Nagoya, Aichi 467-8603, Japan.
PMID: 21227703 DOI: 10.1016/j.bmc.2010.12.024
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.