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

doi:10.1039/c4md00507d

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

Istituto Europeo di Oncologia

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	665-670
Number of pages	6
Journal	MedChemComm
Volume	6
Issue number	4
DOIs	https://doi.org/10.1039/c4md00507d
Publication status	Published - Apr 1 2015

ASJC Scopus subject areas

Biochemistry
Pharmaceutical Science

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Rodriguez, V., Valente, S., Rovida, S., Rotili, D., Stazi, G., Lucidi, A., Ciossani, G., Mattevi, A., Botrugno, O. A., Dessanti, P., Mercurio, C., Vianello, P., Minucci, S., Varasi, M., & Mai, A. (2015). Pyrrole- and indole-containing tranylcypromine derivatives as novel lysine-specific demethylase 1 inhibitors active on cancer cells. MedChemComm, 6(4), 665-670. https://doi.org/10.1039/c4md00507d

Pyrrole- and indole-containing tranylcypromine derivatives as novel lysine-specific demethylase 1 inhibitors active on cancer cells. / Rodriguez, Veronica; Valente, Sergio; Rovida, Stefano; Rotili, Dante; Stazi, Giulia; Lucidi, Alessia; Ciossani, Giuseppe; Mattevi, Andrea; Botrugno, Oronza A.; Dessanti, Paola; Mercurio, Ciro; Vianello, Paola; Minucci, Saverio; Varasi, Mario; Mai, Antonello.

In: MedChemComm, Vol. 6, No. 4, 01.04.2015, p. 665-670.

Research output: Contribution to journal › Article › peer-review

Rodriguez, V, Valente, S, Rovida, S, Rotili, D, Stazi, G, Lucidi, A, Ciossani, G, Mattevi, A, Botrugno, OA, Dessanti, P, Mercurio, C, Vianello, P, Minucci, S, Varasi, M & Mai, A 2015, 'Pyrrole- and indole-containing tranylcypromine derivatives as novel lysine-specific demethylase 1 inhibitors active on cancer cells', MedChemComm, vol. 6, no. 4, pp. 665-670. https://doi.org/10.1039/c4md00507d

Rodriguez, Veronica ; Valente, Sergio ; Rovida, Stefano ; Rotili, Dante ; Stazi, Giulia ; Lucidi, Alessia ; Ciossani, Giuseppe ; Mattevi, Andrea ; Botrugno, Oronza A. ; Dessanti, Paola ; Mercurio, Ciro ; Vianello, Paola ; Minucci, Saverio ; Varasi, Mario ; Mai, Antonello. / Pyrrole- and indole-containing tranylcypromine derivatives as novel lysine-specific demethylase 1 inhibitors active on cancer cells. In: MedChemComm. 2015 ; Vol. 6, No. 4. pp. 665-670.

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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",

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AU - Dessanti, Paola

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AU - Varasi, Mario

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