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 lid (R,1S,2R) were the most potent isomers against LSDI 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 llb and lid inhibited the colony forming potential in murine promyelocytic blasts.
Pure Diastereomers of a Tranylcypromine-Based LSD1 Inhibitor: Enzyme Selectivity and In-Cell Studies
CIOSSANI, GIUSEPPE;MATTEVI, ANDREA;
2015-01-01
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 lid (R,1S,2R) were the most potent isomers against LSDI 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 llb and lid inhibited the colony forming potential in murine promyelocytic blasts.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
