Abstract
The pure four diastereomers (11a-d) of trans-benzyl (1-((4-(2-aminocyclopropyl)phenyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate hydrochloride 11, previously described by us as LSD1 inhibitor, were obtained by enantiospecific synthesis/chiral HPLC separation method. Tested in LSD1 and MAO assays, 11b (S,1S,2R) and 11d (R,1S,2R) were the most potent isomers against LSD1 and were less active against MAO-A and practically inactive against MAO-B. In cells, all the four diastereomers induced Gfi-1b and ITGAM gene expression in NB4 cells, accordingly with their LSD1 inhibition, and 11b and 11d inhibited the colony forming potential in murine promyelocytic blasts.
Original language | English |
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Pages (from-to) | 173-177 |
Number of pages | 5 |
Journal | ACS Medicinal Chemistry Letters |
Volume | 6 |
Issue number | 2 |
DOIs | |
Publication status | Published - Feb 12 2015 |
Keywords
- Epigenetics
- leukemia
- lysine-specific demethylase
- stereoisomers
- tranylcypromine
ASJC Scopus subject areas
- Organic Chemistry
- Drug Discovery
- Biochemistry