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

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. (C) 2010 Elsevier Ltd. All rights reserved.