Pyrrole- and indole-containing tranylcypromine derivatives as novel lysine-specific demethylase 1 inhibitors active on cancer cells†,10.1039/C4MD00507D

热搜：

Lactoyl-CoA 全氟丁基戊烷白叶藤碱全氟己基辛烷新白叶藤碱壳寡糖特色专题-生物多肽

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,Mario Varasi

MedChemComm Pub Date : 12/23/2014 00:00:00 , 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.