Inhibition of FAD-dependent lysine-specific demethylases by chiral polyamine analogues.

ABSTRACT: Lysine-specific demethylases 1 and 2 (LSD1 and LSD2) are flavoenzyme demethylases, and their inhibitors are considered as potential chemical tools and anticancer agents. Here we report polyamine-based inhibitors of LSD1 and LSD2. In the initial screening, partially constrained polyamine 2 which contains three trans-cyclopentane units with a total of six stereogenic centers, showed the most potent LSD1-inhibitory activity. We then prepared a set of optical isomers of 2 and evaluated their inhibitory activities toward LSD1, LSD2, monoamine oxidases A and B (MAO-A and MAO-B). Optical isomers of 2 showed LSD1-inhibitory activity with K _i values of 2.2 to 6.4 μM, and LSD2-inhibitory activity with K _i values of 4.4 to 39 μM; there was a general preferen

SUBMITTER: Umezawa N 

PROVIDER: S-EPMC9088916 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature