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

MedChemComm Pub Date: 2014-12-23 DOI: 10.1039/C4MD00507D

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.

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