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

doi:10.1021/ml500424z

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

Istituto Europeo di Oncologia

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	173-177
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	6
Issue number	2
DOIs	https://doi.org/10.1021/ml500424z
Publication status	Published - Feb 12 2015

Keywords

Epigenetics
leukemia
lysine-specific demethylase
stereoisomers
tranylcypromine

ASJC Scopus subject areas

Organic Chemistry
Drug Discovery
Biochemistry

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10.1021/ml500424z

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Valente, S., Rodriguez, V., Mercurio, C., Vianello, P., Saponara, B., Cirilli, R., Ciossani, G., Labella, D., Marrocco, B., Ruoppolo, G., Botrugno, O. A., Dessanti, P., Minucci, S., Mattevi, A., Varasi, M., & Mai, A. (2015). Pure diastereomers of a tranylcypromine-based LSD1 inhibitor: Enzyme selectivity and in-cell studies. ACS Medicinal Chemistry Letters, 6(2), 173-177. https://doi.org/10.1021/ml500424z

Pure diastereomers of a tranylcypromine-based LSD1 inhibitor : Enzyme selectivity and in-cell studies. / Valente, Sergio; Rodriguez, Veronica; Mercurio, Ciro; Vianello, Paola; Saponara, Bruna; Cirilli, Roberto; Ciossani, Giuseppe; Labella, Donatella; Marrocco, Biagina; Ruoppolo, Giovanni; Botrugno, Oronza A.; Dessanti, Paola; Minucci, Saverio; Mattevi, Andrea; Varasi, Mario; Mai, Antonello.

In: ACS Medicinal Chemistry Letters, Vol. 6, No. 2, 12.02.2015, p. 173-177.

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

Valente, S, Rodriguez, V, Mercurio, C, Vianello, P, Saponara, B, Cirilli, R, Ciossani, G, Labella, D, Marrocco, B, Ruoppolo, G, Botrugno, OA, Dessanti, P, Minucci, S, Mattevi, A, Varasi, M & Mai, A 2015, 'Pure diastereomers of a tranylcypromine-based LSD1 inhibitor: Enzyme selectivity and in-cell studies', ACS Medicinal Chemistry Letters, vol. 6, no. 2, pp. 173-177. https://doi.org/10.1021/ml500424z

Valente, Sergio ; Rodriguez, Veronica ; Mercurio, Ciro ; Vianello, Paola ; Saponara, Bruna ; Cirilli, Roberto ; Ciossani, Giuseppe ; Labella, Donatella ; Marrocco, Biagina ; Ruoppolo, Giovanni ; Botrugno, Oronza A. ; Dessanti, Paola ; Minucci, Saverio ; Mattevi, Andrea ; Varasi, Mario ; Mai, Antonello. / Pure diastereomers of a tranylcypromine-based LSD1 inhibitor : Enzyme selectivity and in-cell studies. In: ACS Medicinal Chemistry Letters. 2015 ; Vol. 6, No. 2. pp. 173-177.

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AU - Ruoppolo, Giovanni

AU - Botrugno, Oronza A.

AU - Dessanti, Paola

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AU - Mattevi, Andrea

AU - Varasi, Mario

AU - Mai, Antonello

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

Abstract

Keywords

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