Pure diastereomers of a tranylcypromine-based LSD1 inhibitor: Enzyme selectivity and in-cell studies

Sergio Valente, Veronica Rodriguez, Ciro Mercurio, Paola Vianello, Bruna Saponara, Roberto Cirilli, Giuseppe Ciossani, Donatella Labella, Biagina Marrocco, Giovanni Ruoppolo, Oronza A. Botrugno, Paola Dessanti, Saverio Minucci, Andrea Mattevi, Mario Varasi, Antonello Mai

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)173-177
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume6
Issue number2
DOIs
Publication statusPublished - Feb 12 2015

Keywords

  • Epigenetics
  • leukemia
  • lysine-specific demethylase
  • stereoisomers
  • tranylcypromine

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

Fingerprint Dive into the research topics of 'Pure diastereomers of a tranylcypromine-based LSD1 inhibitor: Enzyme selectivity and in-cell studies'. Together they form a unique fingerprint.

Cite this