Pyrrole- and indole-containing tranylcypromine derivatives as novel lysine-specific demethylase 1 inhibitors active on cancer cells

Veronica Rodriguez, Sergio Valente, Stefano Rovida, Dante Rotili, Giulia Stazi, Alessia Lucidi, Giuseppe Ciossani, Andrea Mattevi, Oronza A. Botrugno, Paola Dessanti, Ciro Mercurio, Paola Vianello, Saverio Minucci, Mario Varasi, Antonello Mai

Research output: Contribution to journalArticlepeer-review

Abstract

On the basis of previous research showing the capability of N-carbobenzyloxy-(Z-)amino acid-tranylcypromine (-TCPA) derivatives to inhibit LSD1, we inserted at the 4-amino-TCPA moiety first a Z-Pro (9) and a Z-Gly (10) residue and then, after the encouraging data obtained for 9, a pyrrole and an indole ring in which the relative N1 position carried a acetophenone, a N-phenyl/benzylacetamide, or a Z chain (11a-f and 12a-f, respectively). In both series, the Z-pyrrole and indole derivatives 11e, f and 12e, f displayed high LSD1 inhibitory activity. The compounds are able to inhibit LSD1 in NB4 cells, increasing the expression of two related genes, GFI-1b and ITGAM, and to induce cell growth arrest in the AML MB4-11 and APL NB4 cell lines. This journal is

Original languageEnglish
Pages (from-to)665-670
Number of pages6
JournalMedChemComm
Volume6
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

ASJC Scopus subject areas

  • Biochemistry
  • Pharmaceutical Science

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