title: Pure Diastereomers of a Tranylcypromine-Based LSD1 Inhibitor: Enzyme Selectivity and In-Cell Studies.
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.
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of Roma , P.le A. Moro 5, 00185 Roma, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Valente
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of Roma , P.le A. Moro 5, 00185 Roma, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Rodriguez
authors.affiliation: Genextra Group, DAC s.r.l. , Via Adamello 16, 20139 Milano, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Mercurio
authors.affiliation: Dipartimento di Oncologia Sperimentale, IEO-European Institute of Oncology , Via Adamello 16, 20139 Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Vianello
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Italian National Institute of Health , Via Regina Elena 299, 00161 Roma, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Saponara
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Italian National Institute of Health , Via Regina Elena 299, 00161 Roma, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cirilli
authors.affiliation: Department of Biology and Biotechnology, University of Pavia , Via Ferrata 1, 27100 Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ciossani
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of Roma , P.le A. Moro 5, 00185 Roma, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Labella
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of Roma , P.le A. Moro 5, 00185 Roma, Italy.
authors.forename: Biagina
authors.initials: B
authors.lastname: Marrocco
authors.affiliation: Department of Sense Organs, Sapienza University of Roma , P.le A. Moro 5, 00185 Roma, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ruoppolo
authors.affiliation: Dipartimento di Oncologia Sperimentale, IEO-European Institute of Oncology , Via Adamello 16, 20139 Milano, Italy.
authors.forename: Oronza A
authors.initials: OA
authors.lastname: Botrugno
authors.affiliation: Dipartimento di Oncologia Sperimentale, IEO-European Institute of Oncology , Via Adamello 16, 20139 Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Dessanti
authors.affiliation: Dipartimento di Oncologia Sperimentale, IEO-European Institute of Oncology , Via Adamello 16, 20139 Milano, Italy ; Department of Biosciences, University of Milan , 20100 Milan, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Minucci
authors.affiliation: Department of Biology and Biotechnology, University of Pavia , Via Ferrata 1, 27100 Pavia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mattevi
authors.affiliation: Dipartimento di Oncologia Sperimentale, IEO-European Institute of Oncology , Via Adamello 16, 20139 Milano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Varasi
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of Roma , P.le A. Moro 5, 00185 Roma, Italy ; Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University of Roma , P.le A. Moro 5, 00185 Roma, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
keywords: Epigenetics; leukemia; lysine-specific demethylase; stereoisomers; tranylcypromine