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 |
|---|---|
| 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 |
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Keywords
- Epigenetics
- leukemia
- lysine-specific demethylase
- stereoisomers
- tranylcypromine
ASJC Scopus subject areas
- Organic Chemistry
- Drug Discovery
- Biochemistry
Cite this
Pure diastereomers of a tranylcypromine-based LSD1 inhibitor : Enzyme selectivity and in-cell studies. / Valente, Sergio; Rodriguez, Veronica; Mercurio, Ciro; Vianello, Paola; Saponara, Bruna; Cirilli, Roberto; Ciossani, Giuseppe; Labella, Donatella; Marrocco, Biagina; Ruoppolo, Giovanni; Botrugno, Oronza A.; Dessanti, Paola; Minucci, Saverio; Mattevi, Andrea; Varasi, Mario; Mai, Antonello.
In: ACS Medicinal Chemistry Letters, Vol. 6, No. 2, 12.02.2015, p. 173-177.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pure diastereomers of a tranylcypromine-based LSD1 inhibitor
T2 - Enzyme selectivity and in-cell studies
AU - Valente, Sergio
AU - Rodriguez, Veronica
AU - Mercurio, Ciro
AU - Vianello, Paola
AU - Saponara, Bruna
AU - Cirilli, Roberto
AU - Ciossani, Giuseppe
AU - Labella, Donatella
AU - Marrocco, Biagina
AU - Ruoppolo, Giovanni
AU - Botrugno, Oronza A.
AU - Dessanti, Paola
AU - Minucci, Saverio
AU - Mattevi, Andrea
AU - Varasi, Mario
AU - Mai, Antonello
PY - 2015/2/12
Y1 - 2015/2/12
N2 - 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.
AB - 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.
KW - Epigenetics
KW - leukemia
KW - lysine-specific demethylase
KW - stereoisomers
KW - tranylcypromine
UR - http://www.scopus.com/inward/record.url?scp=84922867052&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922867052&partnerID=8YFLogxK
U2 - 10.1021/ml500424z
DO - 10.1021/ml500424z
M3 - Article
AN - SCOPUS:84922867052
VL - 6
SP - 173
EP - 177
JO - ACS Medicinal Chemistry Letters
JF - ACS Medicinal Chemistry Letters
SN - 1948-5875
IS - 2
ER -