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Pure Diastereomers of a Tranylcypromine-Based LSD1 Inhibitor: Enzyme Selectivity and In-Cell Studies.

Authors :
Valente S
Rodriguez V
Mercurio C
Vianello P
Saponara B
Cirilli R
Ciossani G
Labella D
Marrocco B
Ruoppolo G
Botrugno OA
Dessanti P
Minucci S
Mattevi A
Varasi M
Mai A
Source :
ACS medicinal chemistry letters [ACS Med Chem Lett] 2014 Dec 08; Vol. 6 (2), pp. 173-7. Date of Electronic Publication: 2014 Dec 08 (Print Publication: 2015).
Publication Year :
2014

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.

Details

Language :
English
ISSN :
1948-5875
Volume :
6
Issue :
2
Database :
MEDLINE
Journal :
ACS medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
25699146
Full Text :
https://doi.org/10.1021/ml500424z